by Jason Wasserman MD PhD FRCPC and David Li MD
December 12, 2024
This article is designed to help you understand your pathology report for acute myeloid leukemia (AML). Each section explains an important aspect of the diagnosis and what it means for you.
What is acute myeloid leukemia?
Acute myeloid leukemia (AML) is a type of blood cancer that starts in the bone marrow, the soft tissue inside bones that makes blood cells. In acute myeloid leukemia, immature blood cells called blasts grow uncontrollably, preventing the bone marrow from producing normal red blood cells, white blood cells, and platelets. This rapid growth of abnormal cells can spread to other body parts, including the blood, spleen, liver, and brain. Acute myeloid leukemia is called “acute” because it progresses quickly if not treated.
What are the symptoms of acute myeloid leukemia?
The symptoms of acute myeloid leukemia occur because the abnormal cells crowd out the healthy ones in the bone marrow, leading to low blood counts.
Common symptoms include:
- Feeling very tired or weak.
- Bruising or bleeding easily, including frequent nosebleeds or bleeding gums.
- Persistent infections.
- Fever without a clear cause.
- Bone or joint pain.
- Swollen lymph nodes.
- Pale skin.
These symptoms can develop quickly and become severe over days or weeks.
What causes acute myeloid leukemia?
Acute myeloid leukemia happens when the DNA inside bone marrow cells changes, leading to uncontrolled growth. These changes affect the genes that control how cells grow, divide, or die. Some people with acute myeloid leukemia may have risk factors, including specific genetic syndromes, exposure to chemicals, radiation, or previous cancer treatments. In other cases, acute myeloid leukemia develops in people without any apparent risk factors.
How is the diagnosis of acute myeloid leukemia made?
Pathologists diagnose acute myeloid leukemia by examining blood and bone marrow samples. A blood test called a complete blood count (CBC) may show high numbers of blasts (immature cells) or low numbers of normal blood cells. A bone marrow biopsy is often needed to confirm the diagnosis. In this procedure, a small sample of bone marrow is removed and examined under a microscope.
Pathologists use additional tests to identify changes in leukemia cells’ chromosomes, genes, or proteins. These tests help confirm the diagnosis and determine the subtype of acute myeloid leukemia.
What are blasts, and why is the percentage of blasts significant?
Blasts are immature blood cells normally found in very small numbers in the bone marrow, where blood cells are produced. These immature cells are meant to grow and develop into mature red blood cells, white blood cells, or platelets. In most acute myeloid leukemias, the blasts multiply uncontrollably but fail to mature properly. The percentage of blasts is an important indicator of disease severity. Blasts typically comprise less than 5% of the cells in healthy bone marrow. In acute myeloid leukemia, the blast count rises to 20% or higher, which disrupts the production of healthy blood cells and leads to symptoms like fatigue, bleeding, and infections. Monitoring the blast percentage also helps doctors assess how well the disease is responding to treatment.
Subtypes of acute myeloid leukemia
Pathologists divide acute myeloid leukemia into subtypes based on the molecular or genetic changes in the leukemia cells. These changes can include fusions (when two genes merge into one), mutations (alterations in the DNA), or rearrangements (when a part of a gene is relocated). Knowing the subtype is important because it affects both treatment and prognosis. When no specific genetic changes are found, pathologists classify acute myeloid leukemia by looking at how the leukemia cells appear under the microscope. Below are some key subtypes of acute myeloid leukemia, each of which will be explored in detail.
Subtypes with specific molecular changes
Acute promyelocytic leukemia with PML::RARA fusion
Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia that occurs when two genes—PML and RARA—fuse, disrupting normal blood cell development. This fusion blocks the maturation of white blood cells, accumulating abnormal promyelocytes in the bone marrow and blood. APL commonly affects people between the ages of 20 and 59 and accounts for about 5–8% of acute myeloid leukemia cases in younger individuals. Patients with APL may experience symptoms such as fatigue, infections, bleeding, or easy bruising, and they often present with low white blood cell counts (leukopenia). In some cases, however, patients develop very high white blood cell counts, especially in a subtype called microgranular APL.
A key concern in APL is a blood clotting disorder called disseminated intravascular coagulation (DIC). DIC occurs due to a combination of low platelet counts (thrombocytopenia) and excessive breakdown of clots, leading to severe bleeding that can be life-threatening if not managed early. Blood tests often show signs of these clotting problems, and close monitoring during treatment is critical. The diagnosis of APL is confirmed by detecting the PML::RARA fusion through molecular tests or observing abnormal promyelocytes with large granules or bundles of Auer rods—unique needle-shaped structures—under the microscope.
With modern treatment, the prognosis for APL is excellent. Low- and intermediate-risk patients are usually treated with a combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) without the need for traditional chemotherapy. This approach is highly effective, with more than 90% of patients achieving long-term remission. For those with high-risk disease, additional chemotherapy may be used alongside ATRA and ATO. Thanks to these advancements, APL is now considered one of the most curable forms of leukemia.
Acute myeloid leukemia with RUNX1::RUNX1T1 fusion
Acute myeloid leukemia with RUNX1::RUNX1T1 fusion is a subtype of acute myeloid leukemia caused by the fusion of two genes: RUNX1, which regulates normal blood cell development, and RUNX1T1, a gene that limits cell growth. This fusion blocks the maturation of white blood cells, causing immature cells, called blasts, to accumulate in the bone marrow and blood. Acute myeloid leukemia with RUNX1::RUNX1T1 accounts for about 1–5% of acute myeloid leukemia cases, and it is more common in individuals of African-American or East Asian descent. Patients may experience fatigue, persistent infections, easy bruising, and bleeding. Some individuals develop organ enlargement or myeloid sarcomas, solid tumours of immature blood cells outside the bone marrow.
Blood tests for acute myeloid leukemia with RUNX1::RUNX1T1 often reveal high levels of blasts and other immature cells, with some patients showing dysplastic features like abnormal nuclear shapes in neutrophils. Under the microscope, the leukemia cells may contain Auer rods—needle-like structures inside the cytoplasm. These blasts express specific proteins, including CD34 and myeloperoxidase, along with some markers typically seen in lymphoid cells, such as CD19. Additional mutations, particularly in the KIT gene, can influence treatment outcomes and prognosis.
Acute myeloid leukemia with RUNX1::RUNX1T1 generally responds well to intensive chemotherapy, such as high-dose cytarabine. Most patients achieve long-term remission with appropriate treatment. However, individuals with additional risk factors, such as specific genetic mutations or high blast counts after initial therapy, may need more aggressive treatment like stem cell transplants. Ongoing monitoring for residual disease is essential, as early detection of remaining leukemia cells after treatment can help prevent relapse and improve survival.
Acute myeloid leukemia with CBFB::MYH11 fusion
Acute myeloid leukemia with CBFB::MYH11 fusion occurs when two genes, CBFB and MYH11, join together, disrupting normal blood cell development. This genetic fusion interferes with the function of core-binding factor proteins, which are essential for regulating how myeloid cells grow and mature. Acute myeloid leukemia with CBFB::MYH11 makes up 5–8% of acute myeloid leukemia cases, primarily affecting younger individuals, with a higher incidence in people of European ancestry. Patients often experience symptoms like fatigue, easy bruising, infections, and bleeding, and they typically present with elevated white blood cell counts. Some may also develop myeloid sarcomas—solid tumours made up of immature blood cells.
Blood and bone marrow samples from affected patients show an increase in immature cells, often with abnormal eosinophils, a type of white blood cell that contains unusually large, dark purple granules. These samples may also contain blasts expressing markers like CD34, KIT, and myeloperoxidase, along with more mature monocytic cells expressing markers like CD14 and CD64. Molecular tests confirm the CBFB::MYH11 fusion or related chromosomal changes, such as inv(16) or t(16;16). Additional mutations, including changes in the RAS and KIT genes, may influence treatment outcomes.
Acute myeloid leukemia with CBFB::MYH11 typically responds well to chemotherapy regimens that include high-dose cytarabine. During therapy, some patients may also benefit from adding targeted treatments, such as gemtuzumab ozogamicin. Most patients achieve long-term remission, with survival rates of about 50% in adults. However, the presence of specific genetic mutations or incomplete remission after initial treatment may increase the risk of relapse, requiring more intensive therapy. Regular monitoring for minimal residual disease helps identify early signs of relapse and guide further treatment strategies.
Acute myeloid leukemia with DEK::NUP214 fusion
Acute myeloid leukemia with DEK::NUP214 fusion is a rare subtype caused by the fusion of two genes: DEK, which regulates cell growth, and NUP214, which plays a role in transporting molecules within the cell. This fusion interferes with normal protein functions, contributing to the development of leukemia. Acute myeloid leukemia with DEK::NUP214 accounts for about 1% of acute myeloid leukemia cases in adults and 0.6–1.7% in children, with the average age of diagnosis being between 10–13 years in children and 35–51 years in adults. Symptoms often include fatigue, anemia, easy bruising, bleeding, and infections. Some patients may have high white blood cell counts (leukocytosis), while others present with low counts across all blood cells (pancytopenia).
In bone marrow and blood samples, leukemia cells often show abnormal development, including dysplasia—irregular cell shape and structure. Abnormal myeloid cells and blasts may be present, sometimes with features resembling a myelodysplastic neoplasm (MDS). Leukemic cells usually express proteins such as CD13, CD33, CD34, and myeloperoxidase, but other markers like CD7 and CD15 may also be detected. This subtype is confirmed by detecting the fusion gene through molecular tests or identifying the chromosomal abnormality t(6;9). FLT3 mutations, often found in this subtype, are associated with faster relapse but do not significantly impact overall survival.
Acute myeloid leukemia with DEK::NUP214 fusion carries a poor prognosis, with many patients experiencing relapse despite treatment. Median survival for patients with acute myeloid leukemia is around 13 months, and allogeneic stem cell transplantation offers the best chance of improving outcomes. Without a transplant, survival beyond 45 months is rare. Given the aggressive nature of this subtype, early diagnosis and careful monitoring for disease progression are critical. Treatment strategies may include intensive chemotherapy and, in some cases, investigational therapies targeting the FLT3 mutation.
Acute myeloid leukemia with RBM15::MRTFA fusion
Acute myeloid leukemia with RBM15::MRTFA fusion is a rare subtype of acute myeloid leukemia that primarily affects infants and young children. This form of acute myeloid leukemia is characterized by megakaryocytic differentiation, meaning the leukemia cells resemble immature platelet-producing cells. It accounts for fewer than 1% of acute myeloid leukemia cases overall but makes up 10–12% of pediatric cases of acute megakaryoblastic leukemia. Patients often present with an enlarged liver and spleen (hepatosplenomegaly), anemia, low platelet counts (thrombocytopenia), and slightly elevated white blood cell counts. Infants may also show extramedullary disease, with abnormal blood cell growth outside the bone marrow, sometimes leading to conditions like Budd-Chiari syndrome, which affects the liver.
Blood and bone marrow samples from affected individuals typically contain megakaryoblasts—immature cells with round or irregular nuclei and a distinctive basophilic cytoplasm. These cells often lack granules but may have cytoplasmic projections called blebs. Due to fibrosis in the bone marrow, it can be challenging to obtain accurate blast counts, requiring a biopsy for a complete diagnosis. Leukemia cells express platelet markers, such as CD41 and CD61, confirming their megakaryocytic origin. These cells are usually negative for myeloperoxidase and other markers typical of non-megakaryocytic acute myeloid leukemia subtypes.
Acute myeloid leukemia with RBM15::MRTFA fusion has an unpredictable prognosis. Studies suggest varying outcomes, with some showing moderate survival rates and others reporting poorer event-free survival. In pediatric patients, a four-year survival rate of about 70% has been observed. However, additional factors, such as a hyperdiploid karyotype (extra chromosomes), may improve outcomes. Treatment typically involves intensive chemotherapy, and close monitoring is essential due to the risk of relapse. Early diagnosis and molecular confirmation of the RBM15::MRTFA fusion are critical for planning appropriate therapy.
Acute myeloid leukemia with BCR::ABL1 fusion
Acute myeloid leukemia with BCR::ABL1 fusion is a rare subtype of acute myeloid leukemia caused by the fusion of two genes, BCR and ABL1, forming an abnormal protein with continuous tyrosine kinase activity. This subtype arises de novo, meaning it occurs without any preceding chronic myeloid leukemia (CML). Acute myeloid leukemia with BCR::ABL1 accounts for fewer than 0.5% of all acute myeloid leukemia cases and typically affects adults, with a higher occurrence in men. Symptoms often include fatigue, anemia, easy bruising or bleeding, and infections. Patients may also present with high white blood cell counts (leukocytosis), although splenomegaly—commonly seen in CML—is rare in this subtype.
Blood and bone marrow samples reveal increased blasts, often exceeding 20%, with broad variations in cell types, including monocytic or minimally differentiated blasts. These cells express markers such as CD34, CD13, and CD33, which confirm their myeloid origin. Molecular testing identifies the BCR::ABL1 fusion or the related chromosomal abnormality t(9;22). This fusion gene is also associated with other mutations, such as RUNX1 or RAS pathway mutations, which can affect treatment outcomes and complicate the disease course.
Acute myeloid leukemia with BCR::ABL1 carries a poor prognosis, with a median survival time of less than nine months without aggressive treatment. Standard acute myeloid leukemia chemotherapy alone is often ineffective, and tyrosine kinase inhibitors, such as dasatinib, show limited success unless combined with chemotherapy. Allogeneic stem cell transplantation offers the best chance for long-term survival, with studies showing survival rates comparable to those for intermediate-risk acute myeloid leukemia. Early identification and a personalized treatment approach are essential for improving outcomes in this aggressive form of leukemia.
Acute myeloid leukemia with KMT2A rearrangement
Acute myeloid leukemia with KMT2A rearrangement is a type of leukemia caused by alterations in the KMT2A gene located on chromosome 11. This gene can fuse with more than 80 different partner genes, disrupting normal blood cell development and leading to uncontrolled growth of immature cells. This subtype occurs at any age but is especially common in children, accounting for 20% of pediatric acute myeloid leukemia cases and more than 50% of cases in infants. It makes up only 2–3% of acute myeloid leukemia cases in adults. Symptoms include fatigue, infections, bleeding, and high white blood cell counts. Many patients also experience extramedullary involvement, such as gingival swelling, skin lesions, or liver or spleen enlargement.
Blood and bone marrow samples show high levels of immature cells, often with monocytic or myelomonocytic differentiation features. Leukemic cells frequently express markers like CD33, CD65, and HLA-DR, with variable expression of CD34 and KIT. A unique finding in this subtype is the presence of NG2 (CSPG4) on the cell surface. In children, KMT2A rearrangement can present with diverse morphologies, sometimes resembling megakaryoblastic leukemia. Genetic testing confirms the presence of KMT2A rearrangement, and additional mutations, such as those in RAS pathway genes or FLT3, may also be found. These mutations influence treatment response and disease progression.
The prognosis of acute myeloid leukemia with KMT2A rearrangement depends on the specific fusion partner. In adults, patients with KMT2A::MLLT3 fusion have an intermediate risk of relapse, while other KMT2A rearrangements are linked to poorer outcomes. In children, the prognostic significance varies, with some fusions associated with a higher risk of relapse. Treatment involves intensive chemotherapy, and in high-risk cases, allogeneic stem cell transplantation may be required. Early diagnosis and careful genetic monitoring are essential to guide therapy and improve outcomes for patients with this aggressive subtype of acute myeloid leukemia.
Acute myeloid leukemia with MECOM rearrangement
Acute myeloid leukemia with MECOM rearrangement is a rare and aggressive subtype of acute myeloid leukemia characterized by changes in the MECOM gene located on chromosome 3. These rearrangements often involve translocations, such as inv(3) or t(3;3), that disrupt normal blood cell development by overactivating the EVI1 gene, a transcription factor linked to leukemia. Acute myeloid leukemia with MECOM rearrangement affects all age groups but is most common in adults between 18 and 40 years. Symptoms may include anemia, low or high platelet counts, and high white blood cell counts. Hepatosplenomegaly (enlarged liver and spleen) is common, and some patients have increased blasts in the blood or bone marrow.
Blood and bone marrow samples from affected patients often show dysplastic cells, especially abnormal megakaryocytes—platelet-producing cells—which may have small, non-lobated, or bilobed nuclei. Multilineage dysplasia is frequently observed, involving both red and white blood cell precursors. Leukemia cells in this subtype usually express markers like CD34, CD33, CD13, and KIT. Molecular testing confirms the presence of MECOM rearrangements, often involving the translocation inv(3) or t(3;3). Additional mutations, such as those in the RAS pathway or FLT3 gene, are commonly found and can influence disease progression.
Acute myeloid leukemia with MECOM rearrangement has a poor prognosis, with short survival times, regardless of the number of blasts present at diagnosis. The disease is often resistant to conventional chemotherapy, and additional genetic abnormalities, such as monosomy 7 or a complex karyotype, worsen outcomes. Although some cases may respond to intensive treatment, survival remains limited. Early diagnosis, molecular monitoring, and exploring potential stem cell transplantation are essential for managing this aggressive leukemia subtype.
Acute myeloid leukemia with NUP98 rearrangement
Acute myeloid leukemia with NUP98 rearrangement is a subtype of acute myeloid leukemia characterized by translocations involving the NUP98 gene on chromosome 11 and various partner genes. These genetic changes disrupt normal blood cell development and promote leukemia by altering transcription and epigenetic regulation. This subtype occurs more frequently in children, accounting for 2–4.8% of pediatric acute myeloid leukemia cases, and is associated with specific fusion partners such as NUP98::KDM5A in younger children and NUP98::NSD1, which is more common in boys. Symptoms may include fatigue, anemia, easy bruising, and infections, with patients often presenting with elevated white blood cell counts or other signs of abnormal blood production.
Blood and bone marrow samples from patients with NUP98 rearrangement typically show a high blast count, with some cases displaying features of myelomonocytic or monocytic differentiation. Megakaryoblastic differentiation is often observed in younger children, while erythroid differentiation is common in pediatric cases. Leukemia cells usually express markers such as CD34, CD13, CD33, and myeloperoxidase, along with additional markers like CD41 and CD71, reflecting the diversity of cell types involved. Molecular testing is essential, as conventional karyotyping may not always detect NUP98 rearrangements. FISH, RT-PCR, and RNA sequencing are the preferred diagnostic methods for identifying fusions, such as NUP98::NSD1 and NUP98::KDM5A.
Acute myeloid leukemia with NUP98 rearrangement is associated with a poor prognosis, especially in cases with additional FLT3 internal tandem duplication (ITD) mutations, which increase the risk of relapse and reduce survival. This rearrangement is often found in refractory acute myeloid leukemia, complicating treatment for pediatric patients. Allogeneic stem cell transplantation is recommended for patients who achieve remission, as it offers the best chance for long-term survival. Early diagnosis, comprehensive genetic testing, and personalized treatment strategies are essential for managing this aggressive subtype.
Acute myeloid leukemia with NPM1 mutation
Acute myeloid leukemia with NPM1 mutation is a subtype of acute myeloid leukemia characterized by nucleophosmin 1 (NPM1) gene mutations. These mutations cause the NPM1 protein, normally found in the cell nucleus, to accumulate abnormally in the cytoplasm. Acute myeloid leukemia with NPM1 mutation accounts for nearly one-third of adult acute myeloid leukemia cases, with a peak incidence in middle-aged adults and a female predominance. Patients often present with symptoms such as anemia, fatigue, and easy bruising. Many cases show high white blood cell counts, and some patients may also develop myeloid sarcoma—tumour-like collections of leukemia cells outside the bone marrow, involving sites like the skin or lymph nodes.
Blood and bone marrow samples in this subtype usually show increased blasts, often with features of myelomonocytic or monocytic differentiation. A unique characteristic is the presence of blasts with cup-like nuclear morphology, which is highly specific for NPM1 mutation when seen in more than 10% of cells. Leukemia cells frequently express markers such as CD33, KIT (CD117), and myeloperoxidase, with many cases lacking CD34 expression. Molecular testing is essential to confirm the presence of NPM1 mutations, most commonly found in exon 12 of the gene. Additional mutations, such as those in the FLT3, RAS, or DNMT3A genes, often co-occur and can influence disease progression and treatment response.
Acute myeloid leukemia with NPM1 mutation generally has a favorable prognosis, especially in patients without FLT3 internal tandem duplication (ITD) mutations or low FLT3 ITD allele ratios. These patients often respond well to induction chemotherapy. However, those with high FLT3 ITD levels may require more intensive treatment and close monitoring. Molecular testing for residual NPM1 mutations after treatment is important for guiding therapy, as higher levels of the mutated transcript are associated with an increased risk of relapse. In older patients or those with complex genetic profiles, newer treatment strategies, such as hypomethylating agents combined with venetoclax, have shown promising results. Early diagnosis and personalized treatment approaches are essential for optimizing outcomes in this subtype of acute myeloid leukemia.
Acute myeloid leukemia with CEBPA mutation
Acute myeloid leukemia with CEBPA mutation is a distinct subtype of acute myeloid leukemia characterized by mutations in the CEBPA gene, which plays a critical role in myeloid cell development. This condition occurs in two forms: biallelic CEBPA mutation (biCEBPA) or a single mutation confined to the bZIP region of the gene (smbZIP-CEBPA). Both forms are associated with increased white blood cell counts and often affect younger individuals. Patients typically present with symptoms of bone marrow failure, including fatigue, bruising or bleeding, and frequent infections. Some cases of biCEBPA may be linked to an inherited genetic variant, necessitating genetic counseling for affected families.
Blood and bone marrow samples from patients with CEBPA mutations usually show increased immature myeloid cells or blasts, sometimes with evidence of maturation. Dysplasia—abnormal development of blood cells—is common, especially involving granulocytes and megakaryocytes (platelet precursors). Leukemic cells often express markers such as CD13, CD34, and CD33, and many cases also show CD7 expression, which is not typical of most acute myeloid leukemia subtypes. Testing for CEBPA mutations is essential for diagnosis, with next-generation sequencing or PCR-based techniques used to identify both biallelic and bZIP mutations.
Acute myeloid leukemia with CEBPA mutation is generally associated with a favorable prognosis, especially in patients with biCEBPA or smbZIP-CEBPA mutations. These patients tend to respond well to standard induction chemotherapy, and their outcomes are similar to those of individuals with core-binding factor acute myeloid leukemia, which is also considered a favorable-risk subtype. Monitoring for CEBPA mutations provides valuable information for risk stratification and treatment planning. Early diagnosis and personalized treatment approaches are crucial to optimize outcomes, especially for younger patients and those with a familial predisposition.
Acute myeloid leukemia, myelodysplasia-related
Myelodysplasia-related acute myeloid leukemia is a type of acute myeloid leukemia characterized by specific genetic or molecular abnormalities commonly associated with prior myelodysplastic syndromes (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Acute myeloid leukemia-MR can develop either de novo or after a history of these precursor conditions. Patients often present with symptoms caused by bone marrow failure, such as severe fatigue, infections, and bleeding, due to low levels of red blood cells, white blood cells, and platelets (pancytopenia). Although acute myeloid leukemia-MR primarily involves the blood and bone marrow, it can sometimes affect other tissues, resulting in myeloid sarcoma.
Blood and bone marrow examination typically reveals an increase in immature cells called blasts, alongside evidence of abnormal blood cell development, known as multilineage dysplasia. Abnormalities may include neutrophils with underdeveloped or abnormally shaped nuclei, red blood cells with defective maturation, and small or abnormally formed platelet-producing cells called megakaryocytes. Flow cytometry can detect blast cells that express markers such as CD34, KIT (CD117), and HLA-DR. Cytogenetic and molecular testing is crucial for diagnosis, as specific chromosomal abnormalities and gene mutations, including changes in TP53, ASXL1, and SRSF2, are frequently associated with acute myeloid leukemia-MR.
Acute myeloid leukemia-MR has a generally poor prognosis, with lower rates of complete remission compared to other types of acute myeloid leukemia. Treatment options are often guided by the patient’s overall health and the specific mutations present. Some patients with low levels of blasts (oligoblastic acute myeloid leukemia-MR) may benefit from treatment strategies similar to those used for high-risk MDS. Mutations in TP53, commonly seen in acute myeloid leukemia-MR, are associated with worse outcomes, particularly when combined with complex chromosomal changes. Early identification and personalized treatment strategies are essential to improving outcomes for patients with acute myeloid leukemia-MR.
Subtypes without specific molecular changes
Acute myeloid leukemia with minimal differentiation
Acute myeloid leukemia with minimal differentiation is a rare type of acute myeloid leukemia that shows no morphological or cytochemical evidence of myeloid differentiation but can be identified through specific immunophenotypic markers. It typically involves the blood and bone marrow, where an increase in immature white blood cells, or blasts, is observed. This form of acute myeloid leukemia is distinct because it lacks the defining genetic abnormalities seen in other acute myeloid leukemia subtypes. Patients present with symptoms such as fatigue, infections, and bleeding due to low red blood cells, white blood cells, and platelet counts resulting from bone marrow failure.
Most cases occur in adults, with a slight male predominance, and the median age at diagnosis is between 50 and 60 years. Although the exact cause is unknown, recent studies suggest that rearrangements involving the BCL11B gene may sometimes play a role. These rearrangements, such as ZEB2::BCL11B and CDK6::BCL11B, are associated with other mutations, including FLT3 internal tandem duplications (ITD) and changes in epigenetic regulators such as DNMT3A and TET2.
Histologically, the bone marrow is usually hypercellular with sheets of poorly differentiated blasts. These blasts are medium-sized, with round or slightly indented nuclei, and they lack visible granules or Auer rods, typically seen in other acute myeloid leukemia types. On immunophenotyping, the blasts express myeloid-associated markers like CD13, CD33, and CD117, along with stem cell markers such as CD34 and HLA-DR. However, they are negative for myeloperoxidase and other cytochemical stains, which indicates a lack of myeloid differentiation.
Acute myeloid leukemia with minimal differentiation frequently presents with abnormal karyotypes, including trisomies and structural chromosomal changes. Common genetic mutations include RUNX1, ASXL1, and DNMT3A, along with mutations in spliceosome genes such as SRSF2. While the presence of BCL11B rearrangements has been noted, the impact on prognosis remains unclear.
Due to its rarity, data on prognosis and treatment outcomes are limited. Acute myeloid leukemia with minimal differentiation tends to be aggressive, and treatment typically follows protocols similar to those for other types of acute myeloid leukemia. However, identifying underlying genetic changes may provide insights into individualized treatment approaches in the future. Early and accurate diagnosis using immunophenotyping and molecular testing is essential for managing the disease effectively.
Acute myeloid leukemia with maturation
Acute myeloid leukemia with maturation is a subtype of acute myeloid leukemia characterized by myeloid differentiation with granulocytic maturation but lacking specific genetic abnormalities. Patients typically present with fatigue, weakness, and symptoms related to bone marrow failure, such as anemia, thrombocytopenia, and neutropenia. Leukocytosis with increased blasts is frequently observed in blood tests, but monocytic cells comprise less than 20% of bone marrow cells.
Microscopically, the bone marrow is hypercellular, with blasts sometimes containing azurophilic granules or Auer rods. At least 10% of marrow cells show granulocytic maturation, including promyelocytes, myelocytes, and mature neutrophils. Immunohistochemically, blasts express myeloid markers like CD13, CD33, and CD117, along with CD34 and HLA-DR. Markers of granulocytic maturation, such as CD11b, CD15, and CD65, are commonly seen, while monocytic markers like CD14 and CD64 are rare. Blasts are positive for myeloperoxidase and Sudan Black B, but naphthol AS-D chloroacetate esterase is typically negative.
The cause of acute myeloid leukemia with maturation remains unknown. Most cases have a normal karyotype, though some may show trisomies or structural chromosomal abnormalities. Mutations in genes such as ASXL1, RUNX1, and IDH2 are common, while FLT3 mutations are less frequent. Information related to prognosis is limited, but outcomes may vary based on the presence of specific co-occurring mutations.
Acute myeloid leukemia without maturation
Acute myeloid leukemia without maturation is a type of blood cancer where blasts (immature white blood cells) grow uncontrollably but do not mature properly. This condition usually causes symptoms like fatigue, weakness, easy bruising or bleeding, and infections due to low red blood cells, platelets, and healthy white blood cells. Blood tests often show a high number of abnormal blasts circulating in the bloodstream.
Under the microscope, bone marrow samples from these patients show an overgrowth of immature white blood cells with very little development into mature cells. These blasts may have a pale, grey-blue appearance, with some containing tiny structures called Auer rods. Most blasts test positive for proteins that identify them as immature myeloid cells (such as CD13, CD33, and CD117), and some also express proteins like CD34 and HLA-DR. However, the cells usually lack markers for more developed blood cells like monocytes (CD14, CD64) or mature granulocytes (CD15, CD65).
The exact cause of acute myeloid leukemia without maturation is not known. About two-thirds of cases show no major changes in the chromosomes (the structures that carry genes), which is called a “normal karyotype.” In some cases, extra or missing chromosomes may be found. Genetic testing of these leukemia cells may reveal changes in specific genes, such as DNMT3A, RUNX1, or FLT3, affecting disease progress. Doctors use these genetic findings to help guide treatment. The prognosis (the likely outcome) can vary, and more research is needed to fully understand the best ways to treat this type of acute myeloid leukemia.
What does it mean if the bone marrow is described as hypercellular?
When bone marrow is described as hypercellular, it means too many cells are present for the patient’s age. Bone marrow typically contains a mix of developing blood and fat cells. In hypercellular bone marrow, this balance shifts, and there are more developing blood cells than usual. In acute myeloid leukemia, the bone marrow becomes hypercellular because of the rapid accumulation of blasts, which crowd out the healthy cells. This can lead to low counts of functioning red blood cells, white blood cells, and platelets, causing symptoms like anemia, infections, and bleeding.
What does it mean if the bone marrow is described as normocellular?
Normocellular bone marrow has the expected ratio of cells to fat for a person’s age. About 30–50% of adult bone marrow should contain developing blood cells, with the rest comprising fat cells. A normocellular marrow means the bone marrow is functioning as expected, without an excess or deficiency of cells. Finding normocellular marrow during or after treatment can be a positive sign in people with acute myeloid leukemia, indicating that the bone marrow is recovering and producing healthy blood cells.
What does trilineage hematopoiesis mean, and why is it important?
Trilineage hematopoiesis refers to the normal production of all three major types of blood cells: red blood cells (which carry oxygen), white blood cells (which fight infections), and platelets (which help blood clot). In healthy bone marrow, all three of these blood cell types are produced in the right amounts. When acute myeloid leukemia disrupts trilineage hematopoiesis, the body cannot maintain normal levels of these cells, leading to symptoms like anemia, infections, and easy bruising or bleeding. Evaluating trilineage hematopoiesis helps doctors understand whether the bone marrow is functioning normally or has been affected by leukemia or other bone marrow disorders.
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