Acute myeloid leukaemia –⁠ how the approach to diagnosis, risk stratification, and treatment options has changed

Czech version

Authors: P. Žák
Authors‘ workplace: IV. interní hematologická klinika FN Hradec Králové
Published in: Transfuze Hematol. dnes,32, 2026, No. 1, p. 9-15.
Category: Review/Educational Papers
doi: https://doi.org/10.48095/cctahd202606

Overview

New findings in molecular biology have led to a better understanding of the diverse biological behaviour of acute myeloid leukaemia (AML). Based on molecular alterations, classification systems and diagnostic criteria have been modified to better reflect the biological nature of AML. The identification of molecular changes has also enabled more precise prognostic stratification and improved monitoring of treatment response. At the same time, targeted therapies are being developed. The most important drugs in this group include BCL-2 protein inhibitors (venetoclax), FLT3 mutation inhibitors, and IDH1/2 inhibitors. The treatment of AML is complex, highlighting the need for specialised expertise to ensure optimal therapy and achieve the best possible outcomes. Different subtypes of AML require different therapeutic approaches. This review summarises key developments in diagnosis, emphasises the importance of precise molecular genetic testing, and outlines new directions in treatment.

Keywords:

venetoclax – AML (diagnosis) – AML (therapy) – MRD (measurable residual disease) in AML

Sources

1. Khoury JD, Solary E, Abla O, et al. The 5th Edition of the World Health Organizator Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022; 36 (7): 1703–1719.

2. Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemia: Integrating Morphological, Clinical, and Genomic Data. Blood. 2022; 140 : 1200–1228.

3. Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and Management of AML in Adults: 2022 Recommendations From an International Expert Panel on Behalf of the ELN. Blood. 2022; 140 (12): 1345–1377.

4. Short NJ, Zhou S, Fu C, et al. Association of Measurable Residual Disease With Survival Outcomes in Patients With Acute Myeloid Leukemia. JAMA Oncol. 2020; 6 (12): 1890.

5. Estey E, Hasserjian RP, Döhner H. Distinguishing AML From MDS: A Fixed Blast Percentage May No Longer Be Optimal. Blood. 2022; 139 (3): 323–332.

6. Heuser M, Freeman SD, Ossenkoppele GJ, et al. 2021 Update on MRD in Acute Myeloid Leukemia: A Consensus Document From the European LeukemiaNet MRD Working Party. Blood. 2021; 138 (26): 2753–2767.

7. Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic Classification and Prognosis in Acute Myeloid Leukemia. New Engl J Med. 2016; 374 (23): 2209–2221.

8. Lindsley RC, Mar BG, Mazzola F, et al. Acute Myeloid Leukemia Ontogeny Is Defined by Distinct Somatic Mutations. Blood. 2015; 125 (9): 1367–1376.

9. Angenendt L, Röllig C, Montesinos P, et al. Chromosomal Abnormalities and Prognosis in NPM1−Mutated Acute Myeloid Leukemia: A Pooled Analysis of Individual Patient Data From Nine International Cohorts. J Clin Oncol. 2019; 37 (29): 2632–2642.

10. Chan O, Al Ali N, Tashkandi H, et al. Mutations Highly Specific for Secondary AML Are Associated With Poor Outcomes in ELN Favorable Risk NPM1-Mutated AML. Blood Adv. 2024; 8 (5): 1075–1083.

11. Kayser S, Hills RK, Langova R, et al. Characteristics and Outcome of Patients With Acute Myeloid Leukaemia and t (8; 16) (p11; p13): Results From an International Collaborative Study. Br J Haematol. 2021; 192 (5): 832–842.

12. Döhner H, Pratz RW, DiNardo CD, et al. Genetic Risk Stratification and Outcomes Among Treatment -⁠ Naive Patients With AML Treated With Venetoclax and Azacitidine. Blood. 2024; 144 (21): 2211–2222.

13. Bataller A, Bazinet A, DiNardo CD, et al. Prognostic Risk Signature in Patients With Acute Myeloid Leukemia Treated With Hypomethylating Agents and Venetoclax. Blood Adv. 2024; 8 (4): 927–935.

14. Döhner H, DiNardo CD, Appelbaum FR, et al. Genetic risk classification for adults with AML receiving less-intensive therapies: the 2024 ELN recommendations. Blood. 2024; 144 (21): 2169–2173.

15. Othman J, Tiong IS, O‘Nions J, et al. Molecular MRD Is Strongly Prognostic in Patients With NPM1-Mutated AML Receiving Venetoclax-Based Nonintensive Therapy. Blood. 2024; 143 (4): 336–341.

16. Rollig C, Kramer M, Schliemann C, et al. Does Time from Diagnosis to Treatment Affect the Prognosis of Patients with Newly Diagnosed Acute Myeloid Leukemia? Blood. 2020; 136 (7): 823–830.

17. Shimony S, Stahl M, Stone R. Acute Myeloid Leukemia: 2025 Update on Diagnosis, Risk-Stratification, and Management. Am J Hematol. 2025; 100 : 860–891.

18. Yates JW, Wallace HJ, Ellison RR, et al. Cytosine Arabinoside (NSC-63878) and Daunorubicin (NSC-83142) Therapy in Acute Nonlymphocytic Leukemia. Cancer Chemother Rep. 1973; 57 (4): 485–488.

19. Rollig C, Steffen B, Schliemann C, et al. Single or Double Induction With 7 + 3 Containing Standard or High -⁠ Dose Daunorubicin for Newly Diagnosed AML: The Randomized DaunoDouble Trial by the Study Alliance Leukemia. J Clin Oncol. 2024; 43 : 65–74.

20. Halpern AB, Othus M, Huebner EH, et al. Phase 1/2 Trial of GCLAM With Dose -⁠ Escalated Mitoxantrone for Newly Diagnosed AML or Other High-Grade Myeloid Neoplasms. Leukemia. 2018; 32 (11): 2352–2362.

21. DiNardo CD, Lachowiez CA, Takahashi K, et al. Venetoclax Combined With FLAG -⁠ IDA Induction and Consolidation in Newly Diagnosed Acute Myeloid Leukemia. Am J Hematol. 2022; 97 (8): 1035–1043.

22. DiNardo D, Wei-Ying J, Takahashi K, et al. Long Term Results of Venetoclax Combined with FLAG-IDA Induction and Consolidation for Newly Diagnosed and Relapsed or Refractory Acute Myeloid Leukemia. Leukemia. 2025; 39 (4): 854–863.

23. McKoy JM, Angelotta C, Bennett CL, et al. Gemtuzumab Ozogamicin-Associated Sinusoidal Obstructive Syndrome (SOS): An Overview From the Research on Adverse Drug Events and Reports (RADAR) Project. Leukemia Res. 2007; 31 (5): 599–604.

24. Fournier E, Duployez N, Ducourneau B, et al. Mutational Profile and Benefit of Gemtuzumab Ozogamicin in Acute Myeloid Leukemia. Blood. 2020; 135 (8): 542–546.

25. Burnett AK, Hills RK, Milligan D, et al. Identification of Patients With Acute Myeloblastic Leukemia Who Benefit From the Addition of Gemtuzumab Ozogamicin: Results of the MRC AML15 Trial. J Clin Oncol 2011; 29 (4): 369–377.

26. Burnett AK, Russell NH, Hills RK, et al. Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy Improves Survival in Older Patients With Acute Myeloid Leukemia. J Clin Oncol. 2012; 30 (32): 3924–3931.

27. Ronnacker J, Muller PJ, Mikesch JH, et al. Gemtuzumab Ozogamicin in First-Line Treatment of CBF-AML: Insights From a Retrospective Multi-Center Analysis. Leukemia. 2025; 39 : 2174–2180.

28. Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin Plus Chemotherapy for Acute Myeloid Leukemia With a FLT3 Mutation. New Engl J Med. 2017; 377 (5): 454–464.

29. Döhner H, Weber D, Krzykalla J, et al. Midostaurin Plus Intensive Chemotherapy for Younger and Older Patients with AML and FLT3 Internal Tandem Duplications, Blood Adv. 2022; 6 (18): 5345–5355.

30. Erba HP, Montesinos P, Kim HJ, et al. Quizartinib Plus Chemotherapy in Newly Diagnosed Patients With FLT3-Internal-Tandem-Duplication-Positive Acute Myeloid Leukaemia (QuANTUM-First): A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. Lancet. 2023; 401 (10388): 1571–1583.

31. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3 -⁠ Mutated AML. New Engl J Med. 2019; 381 (18): 1728–1740.

32. Wang ES, Goldberg AD, Tallman M, et al. Crenolanib and Intensive Chemotherapy in Adults With Newly Diagnosed FLT3-Mutated AML. J Clin Oncol. 2024; 42 (15): 1776–1787.

33. Lindsley RC, Gibson CJ, Murdock HM, et al. Genetic Characteristics and Outcomes by Mutation Status in a Phase 3 Study of CPX -⁠ 351 Versus 7 + 3 in Older Adults With Newly Diagnosed, High-Risk/Secondary Acute Myeloid Leukemia (AML). Blood. 2019; 134 (Suppl 1): 15.

34. Shimony S, Bewersdorf JP, Shallis RM, et al. Hypomethylating Agents Plus Venetoclax Compared With Intensive Induction Chemotherapy Regimens in Molecularly Defined Secondary AML. Leukemia. 2024; 38 (4): 762–768.

35. Wang H, Mao L, Yang M, et al. Venetoclax Plus 3 + 7 Daunorubicin and Cytarabine Chemotherapy as First -⁠ Line Treatment for Adults With Acute Myeloid Leukaemia: A Multicentre, Single-Arm, Phase 2 Trial. Lancet Haematol. 2022; 9 (6): e415–e424.

36. Kadia TM, Reville PK, Borthakur G, et al. Venetoclax Plus Intensive Chemotherapy With Cladribine, Idarubicin, and Cytarabine in Patients With Newly Diagnosed Acute Myeloid Leukaemia or High-Risk Myelodysplastic Syndrome: A Cohort From a Single-Centre, Single-Arm, Phase 2 Trial. Lancet Haematol. 2021; 8 (8): e552–e561.

37. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. New Engl J Med. 2020; 383 (7): 617–629.

38. Wei H, Montesinos P, Ivanov V, et al. Venetoclax Plus LDAC for Newly Diagnosed AML Ineligible for Intensive Chemotherapy: A Phase 3 Randomized Placebo-Controlled Trial. Blood. 2020; 135 (24): 2137–2145.

39. Wei AH, Panayiotidis P, Montesinos P, et al. 6-Month Follow-Up of VIALE-C Demonstrates Improved and Durable Efficacy in Patients With Untreated AML Ineligible for Intensive Chemotherapy. Blood Cancer J. 2021; 11 (10): 163.

40. Pollyea DA, Winters A, McMahon C, et al. Venetoclax and Azacitidine Followed by Allogeneic Transplant Results in Excellent Outcomes and May Improve Outcomes Versus Maintenance Therapy Among Newly Diagnosed AML Patients Older Than 60. Bone Marrow Transplant. 2022; 57 (2): 160–166.

41. Lübbert M, Wijermans PW, Kicinski M, et al. 10-Day Decitabine Versus 3 + 7 Chemotherapy Followed by Allografting in Older Patients With Acute Myeloid Leukaemia: An Open-Label, Randomised, Controlled, Phase 3 Trial. Lancet Haematol. 2023; 10 (11): e879–e889.

42. Kim K, Maiti A, Loghavi S, et al. Outcomes of TP53-Mutant Acute Myeloid Leukemia With Decitabine and Venetoclax. Cancer. 2021; 127 (20): 3772–3781.

43. Pei S, Pollyea DA, Gustafson A, et al. Monocytic Subclones Confer Resistance to Venetoclax-Based Therapy in Patients With Acute Myeloid Leukemia. Cancer Disc. 2020; 10 (4): 536–551.

44. DiNardo CD, Tiong IS, Quaglieri A, et al. Molecular Patterns of Response and Treatment Failure After Frontline Venetoclax Combinations in Older Patients With AML. Blood. 2020; 135 (11): 791–803.

45. Shimony S, Garcia JS, Keating J, et al. Molecular Ontogeny Underlies the Benefit of Adding Venetoclax to Hypomethylating Agents in Newly Diagnosed AML Patients. Leukemia. 2024; 38 (7): 1494–1500.

46. Lachowiez CA, Loghavi S, Zeng Z, et al. A Phase Ib/II Study of Ivosidenib With Venetoclax +/ −⁠ Azacitidine in IDH1 -⁠ Mutated Myeloid Malignancies. Blood Cancer Disc. 2023; 4 (4): 276–293.

47. Venugopal S, Takahashi K, Daver N, et al. Efficacy and Safety of Enasidenib and Azacitidine Combination in Patients With IDH2 Mutated Acute Myeloid Leukemia and Not Eligible for Intensive Chemotherapy. Blood Cancer J. 2022; 12 (1): 10.

48. Daver N, Short NJ, Macaron W, et al. Azacitidine, Venetoclax, and Gilteritinib in Newly Diagnosed and Relapsed or Refractory FLT3-Mutated AML. J Clin Oncol. 2024; 42 (13): 1499–1508.

49. Fathi A, Perl A, Fell G, et al. Results from PARADIGM –⁠ a Phase 2 Randomized Multi-Center Study Comparing Azacitidine and Venetoclax to Conventional Induction Chemotherapy for Newly Diagnosed Fit Adults with Acute Myeloid Leukemia. 2024; 146 (Suppl 1): 6.

Prohlášení o konfliktu zájmů

Příprava rukopisu byla iniciována firmou Abbvie. Jiný konflikt zájmů v souvislosti s rukopisem nedeklaruji. Poradenská činnost a konzultační činnost v posledních 5 letech: Swixx Biopharma, Abbvie, Novartis, Takeda, Roche, Astellas, Sanofi, Medac, Pfizer, Sanofi, Sobi, Sysmex

Poděkování

Práce byla podpořena programem Cooperatio –⁠ výzkumná oblast hematologie a onkologie a Agenturou pro zdravotnický výzkum MZ ČR č. NU23-03-00562.

Prohlášení o použití AI

AI byla použita k přípravě anglického souhrnu.

Do redakce doručeno dne: 10. 11. 2025.

Přijato po recenzi dne: 1. 2. 2026.

prof. MUDr. Pavel Žák, Ph.D.

IV. interní hematologická klinika

FN HK Sokolská 581

Hradec Králové

LF HK, UK Praha

Šimkova 870 Hradec Králové