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PubMed This is a summary of 21 peer-reviewed journal articles Updated
Hematology

Biology & Diagnosis

At a Glance

Acute myeloid leukemia (AML) is diagnosed through a bone marrow biopsy and aspiration. Doctors look for an accumulation of immature blood cells called blasts, often using a 20% threshold, along with specific genetic mutations to confirm the diagnosis and distinguish it from other blood cancers.

To understand Acute Myeloid Leukemia (AML), it helps to think of your bone marrow as a construction site that has suddenly stopped following the blueprints. Instead of building mature, functional blood cells, the marrow is being overrun by “half-finished” cells called blasts. These immature cells cannot do the jobs of healthy blood cells, and they quickly crowd out the space needed for anything else to grow [1][2].

The Biology of “Double Trouble”

Scientists often describe the cause of AML using a two-hit hypothesis [3]. For leukemia to develop, a normal stem cell usually undergoes a series of genetic “accidents” or mutations that happen in a specific sequence:

  1. The First Hit (Epigenetic/Foundational Changes): Often, the first step involves mutations that change the “switches” (epigenetics) of the cell [4][5]. This makes the cell more likely to live longer than it should and sets the stage for more mutations to occur [6].
  2. The Second Hit (Growth and Maturation Failure): Additional mutations then occur that cause two major problems. Some (Class I) tell the cell to grow and divide uncontrollably, while others (Class II) completely block the cell from maturing into a useful blood cell [3][7].

The result is a massive population of clones—cells that are stuck in an immature state and are multiplying without a “stop” signal [8][9].

The Diagnostic Process: The “Gold Standard”

To confirm a diagnosis of AML, doctors must look directly at the source: your bone marrow. This is done through a bone marrow aspiration and biopsy [10].

  • Aspiration: A small sample of the liquid part of the marrow is drawn into a syringe. This liquid is used for detailed genetic and molecular testing [11].
  • Biopsy: A small, solid core of the bone marrow is removed. This allows doctors to see the “architecture” of the marrow and check for things like scarring or clusters of cancer cells that might be missed in the liquid [12][10].

The “20% Rule” and Modern Exceptions

For decades, the standard requirement for an AML diagnosis was finding that blasts made up at least 20% of the cells in the bone marrow or blood [10]. However, as our understanding of genetics has improved, this rule has changed.

Modern guidelines (such as the WHO 2022 and ICC 2022 classifications) now recognize that the type of mutation can be more important than the number of blasts, though these two systems occasionally use slightly different blast thresholds (e.g., 10% vs 20%) for certain genetic markers [13][14]. If you have certain “defining” genetic abnormalities—such as t(8;21), inv(16), or the NPM1 mutation—you may be diagnosed with AML even if your blast count is much lower than 20% [13][15][16].

Differentiating the “Look-Alikes”

Because several blood disorders can look similar, doctors use a technology called flow cytometry to identify the specific “ID tags” (markers) on the surface of the cells [17]. This helps distinguish AML from other conditions:

  • Acute Lymphoblastic Leukemia (ALL): While AML involves the “myeloid” family of blood cells, ALL involves “lymphoid” cells [17]. Flow cytometry looks for markers like MPO or CD33 to confirm it is AML, or markers like CD19 or CD3 to confirm it is ALL [17][18].
  • Myelodysplastic Syndromes (MDS): Often called a “pre-leukemia,” MDS is a condition where the marrow is failing but the blast count is typically below the thresholds used for AML [19]. While MDS and AML are related, AML is generally more aggressive and requires more intensive treatment [20][21].

By identifying the exact biological “hits” and markers involved, your team can move from a general diagnosis to a precise treatment plan tailored to your specific disease [13].

Common questions in this guide

How is acute myeloid leukemia (AML) diagnosed?
Doctors diagnose AML using a bone marrow aspiration and biopsy. They examine the liquid and solid parts of your marrow for immature cancer cells, called blasts, and look for specific genetic mutations that drive the disease.
What is the 20% rule in AML diagnosis?
Traditionally, an AML diagnosis required finding that at least 20 percent of the cells in the bone marrow or blood were blasts. However, modern guidelines allow for a diagnosis with fewer blasts if certain defining genetic mutations are present.
What is the difference between AML and ALL?
AML involves the myeloid family of blood cells, while ALL involves the lymphoid cells. Doctors use a test called flow cytometry to look for specific cellular markers, like MPO for AML or CD19 for ALL, to tell them apart.
What causes acute myeloid leukemia to develop?
Scientists often describe AML development as a two-hit process. First, foundational genetic mutations occur that allow cells to live longer, followed by a second set of mutations that cause cells to multiply rapidly and fail to mature into healthy blood cells.
What is flow cytometry used for in leukemia?
Flow cytometry is a laboratory test that identifies specific markers on the surface of cells. It helps doctors distinguish AML from other similar blood disorders like ALL or myelodysplastic syndromes to ensure you get the right treatment.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What was the final 'blast' percentage in my bone marrow and blood?
  2. 2.Do I have any 'defining' genetic mutations that confirm an AML diagnosis regardless of the blast count?
  3. 3.How did my flow cytometry results distinguish this from Acute Lymphoblastic Leukemia (ALL)?
  4. 4.Are there signs of Myelodysplastic Syndrome (MDS) in my biopsy, or is this considered 'de novo' AML?
  5. 5.Can you explain which specific mutations in my case are driving the growth versus the failure to mature?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (21)
  1. 1

    Mapping and targeting of the leukemic microenvironment.

    Witkowski MT, Kousteni S, Aifantis I

    The Journal of experimental medicine 2020; (217(2)) doi:10.1084/jem.20190589.

    PMID: 31873722
  2. 2

    Acute Coronary Syndrome in Acute Myeloid Leukemia with Maturation Accompanying Megakaryocytic Differentiation.

    Odani K, Abe J, Tsuyuki Y, et al.

    Case reports in pathology 2020; (2020()):8886298 doi:10.1155/2020/8886298.

    PMID: 33014496
  3. 3

    FLT3 Mutations in Acute Myeloid Leukemia: Unraveling the Molecular Mechanisms and Implications for Targeted Therapies.

    Jalte M, Abbassi M, El Mouhi H, et al.

    Cureus 2023; (15(9)):e45765 doi:10.7759/cureus.45765.

    PMID: 37872917
  4. 4

    Biologico-clinical significance of DNMT3A variants expression in acute myeloid leukemia.

    Lin N, Fu W, Zhao C, et al.

    Biochemical and biophysical research communications 2017; (494(1-2)):270-277 doi:10.1016/j.bbrc.2017.10.041.

    PMID: 29024628
  5. 5

    JAK2-mutated acute myeloid leukemia: comparison of next-generation sequencing (NGS) and single nucleotide polymorphism array (SNPa) findings between two cases.

    de Noronha TR, Mitne-Neto M, Chauffaille ML

    Autopsy & case reports 2019; (9(2)):e2018084 doi:10.4322/acr.2018.084.

    PMID: 31086779
  6. 6

    [Research Advances of IDH2 Gene Mutation in Acute Myeloid Leukemia].

    Zhao YX, Shen XL

    Zhongguo shi yan xue ye xue za zhi 2016; (24(2)):632-6 doi:10.7534/j.issn.1009-2137.2016.02.061.

    PMID: 27151043
  7. 7

    Metabolomic profile of acute myeloid leukaemia parallels of prognosis and response to therapy.

    Bolkun L, Pienkowski T, Sieminska J, et al.

    Scientific reports 2023; (13(1)):21809 doi:10.1038/s41598-023-48970-0.

    PMID: 38071228
  8. 8

    Gilteritinib in the treatment of relapsed and refractory acute myeloid leukemia with a FLT3 mutation.

    Chew S, Mackey MC, Jabbour E

    Therapeutic advances in hematology 2020; (11()):2040620720930614 doi:10.1177/2040620720930614.

    PMID: 32547718
  9. 9

    Identification of U937JAK3-M511I Acute Myeloid Leukemia Cells as a Sensitive Model to JAK3 Inhibitor.

    Si H, Wang J, He R, et al.

    Frontiers in oncology 2021; (11()):807200 doi:10.3389/fonc.2021.807200.

    PMID: 35111683
  10. 10

    Immunohistochemistry in Acute Myeloid Leukemia.

    Cruise MW

    Methods in molecular biology (Clifton, N.J.) 2017; (1633()):33-49 doi:10.1007/978-1-4939-7142-8_3.

    PMID: 28735479
  11. 11

    An Extensive Analysis and Comparison of Bone Marrow Aspiration and Bone Marrow Trephine Biopsy at a Tertiary Care Hospital in Jharkhand for Various Hematological and Non-hematological Illnesses.

    Jawed MA, Paswan MK, Mahto SK, et al.

    Cureus 2024; (16(6)):e62661 doi:10.7759/cureus.62661.

    PMID: 39036242
  12. 12

    Coexistence of Acute Myeloid Leukemia and B-cell Non-Hodgkin Lymphoma Diagnosed on a Bone Marrow Trephine Biopsy.

    Ahmad N, Asif H, Burhan M, et al.

    Cureus 2025; (17(3)):e81107 doi:10.7759/cureus.81107.

    PMID: 40271335
  13. 13

    Comparative Analysis of AML Classification Systems: Evaluating the WHO, ICC, and ELN Frameworks and Their Distinctions.

    Salman H

    Cancers 2024; (16(16)) doi:10.3390/cancers16162915.

    PMID: 39199685
  14. 14

    Advances towards genome-based acute myeloid leukemia classification: A comparative analysis of WHO-HAEM4R, WHO-HAEM5, and International Consensus Classification.

    Chen X, Yuan L, Zhang Y, et al.

    American journal of hematology 2024; (99(5)):824-835 doi:10.1002/ajh.27249.

    PMID: 38321864
  15. 15

    What is new in acute myeloid leukemia classification?

    Park HS

    Blood research 2024; (59(1)):15 doi:10.1007/s44313-024-00016-8.

    PMID: 38616211
  16. 16

    Multimodal and Data-Driven Assessment of Myeloid Neoplasms Refines Classification across Disease States.

    Lachowiez CA, Asimomitis G, Bernard E, et al.

    Blood cancer discovery 2025; (6(5)):425-436 doi:10.1158/2643-3230.BCD-25-0047.

    PMID: 40608896
  17. 17

    Aberrant expression of CD markers in patients with acute leukemia.

    Habeeb AR, Al-Tameemi H, Abdullah DAA, et al.

    Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego 2025; (53(6)):734-741 doi:10.36740/Merkur202506104.

    PMID: 41554067
  18. 18

    Applicability of a single 5 color cytoplasmic markers tube as primary panel for immunophenotyping of acute leukemia: A Gujarat Cancer and Research Institute experience.

    Parikh BP, Patel SP, Raiya BN, et al.

    Indian journal of cancer 2016; (53(3)):349-352 doi:10.4103/0019-509X.200659.

    PMID: 28244454
  19. 19

    Acute Myeloid Leukemia Arising from Myelodysplastic Syndromes.

    Kwon A, Weinberg OK

    Clinics in laboratory medicine 2023; (43(4)):657-667 doi:10.1016/j.cll.2023.07.001.

    PMID: 37865509
  20. 20

    Comparison of myeloid blast counts and variant allele frequencies of gene mutations in myelodysplastic syndrome with excess blasts and secondary acute myeloid leukemia.

    Chen X, Othus M, Wood BL, et al.

    Leukemia & lymphoma 2021; (62(5)):1226-1233 doi:10.1080/10428194.2020.1861267.

    PMID: 33345655
  21. 21

    What biologic factors predict for transformation to AML?

    Bejar R

    Best practice & research. Clinical haematology 2018; (31(4)):341-345 doi:10.1016/j.beha.2018.10.002.

    PMID: 30466744

This page explains the biology and diagnosis of acute myeloid leukemia (AML) for educational purposes. It does not replace professional medical advice or diagnostic interpretation from your hematologist or oncologist.

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