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The new diagnostic criteria for myelodysplasia-related acute myeloid leukemia is useful for predicting clinical outcome: comparison of the 4th and 5th World Health Organization classifications

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Abstract

Mutations in myelodysplasia-related (MR) genes, rather than morphological features, have been included in the diagnostic criteria of the new 5th World Health Organization (WHO) classification for myelodysplastic syndrome (MDS)-associated acute myeloid leukemia (AML). This study compares the clinical relevance of the new criteria with those of the previous version. In a cohort of 135 patients with newly diagnosed AML, the MDS-related AML patients were classified according to the 5th and 4th edition of the WHO classification (AML, myelodysplasia-related [AML-MR5th] and AML with myelodysplasia-related changes [AML-MRC4th], respectively). The median age of the patients was 70.4 years. MR gene mutations were found in 48 patients (35.6%). Sixty-one patients (46.6%) were diagnosed with AML-MRC4th, while 71 patients (53.0%) were diagnosed with AML-MR5th. Patients with AML-MR5th were significantly older with significantly lower treatment response rate, higher recurrence rate, and shorter relapse-free survival after chemotherapy, whereas AML-MRC4th patients did not show any association with the treatment outcome. Overall, the following prognostic factors for survival were identified: age over 75 years, antecedent MDS or MDS/myeloproliferative neoplasm, chromosome 5 or 7 abnormalities, and KRAS and ZSZR2 mutations. The 5th WHO classification is more useful for predicting the treatment response of patients with AML-MR than the previous version. Among the MR genes, ZSZR2 mutations were found to be independent prognostic factors affecting survival.

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References

  1. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405. https://doi.org/10.1182/blood-2016-03-643544

    Article  CAS  PubMed  Google Scholar 

  2. Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G, Van Loo P, Martincorena I, Ganly P, Mudie L, McLaren S, O’Meara S, Raine K, Jones DR, Teague JW, Butler AP, Greaves MF, Ganser A, Dohner K, Schlenk RF, Dohner H, Campbell PJ (2016) Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 374(23):2209–2221. https://doi.org/10.1056/NEJMoa1516192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Arber DA, Erba HP (2020) Diagnosis and treatment of patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). Am J Clin Pathol 154(6):731–741. https://doi.org/10.1093/ajcp/aqaa107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Miesner M, Haferlach C, Bacher U, Weiss T, Macijewski K, Kohlmann A, Klein HU, Dugas M, Kern W, Schnittger S, Haferlach T (2010) Multilineage dysplasia (MLD) in acute myeloid leukemia (AML) correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: a comparison of 408 cases classified as “AML not otherwise specified" (AML-NOS) or "AML with myelodysplasia-related changes” (AML-MRC). Blood 116(15):2742–2751. https://doi.org/10.1182/blood-2010-04-279794

    Article  CAS  PubMed  Google Scholar 

  5. Falini B, Macijewski K, Weiss T, Bacher U, Schnittger S, Kern W, Kohlmann A, Klein HU, Vignetti M, Piciocchi A, Fazi P, Martelli MP, Vitale A, Pileri S, Miesner M, Santucci A, Haferlach C, Mandelli F, Haferlach T (2010) Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1). Blood 115(18):3776–3786. https://doi.org/10.1182/blood-2009-08-240457

    Article  CAS  PubMed  Google Scholar 

  6. Bacher U, Schnittger S, Macijewski K, Grossmann V, Kohlmann A, Alpermann T, Kowarsch A, Nadarajah N, Kern W, Haferlach C, Haferlach T (2012) Multilineage dysplasia does not influence prognosis in CEBPA-mutated AML, supporting the WHO proposal to classify these patients as a unique entity. Blood 119(20):4719–4722. https://doi.org/10.1182/blood-2011-12-395574

    Article  CAS  PubMed  Google Scholar 

  7. Duchmann M, Wagner-Ballon O, Boyer T, Cheok M, Fournier E, Guerin E, Fenwarth L, Badaoui B, Freynet N, Benayoun E, Lusina D, Garcia I, Gardin C, Fenaux P, Pautas C, Quesnel B, Turlure P, Terre C, Thomas X, Lambert J, Renneville A, Preudhomme C, Dombret H, Itzykson R, Cluzeau T (2022) Machine learning identifies the independent role of dysplasia in the prediction of response to chemotherapy in AML. Leukemia 36(3):656–663. https://doi.org/10.1038/s41375-021-01435-7

    Article  CAS  PubMed  Google Scholar 

  8. Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, Bejar R, Berti E, Busque L, Chan JKC, Chen W, Chen X, Chng WJ, Choi JK, Colmenero I, Coupland SE, Cross NCP, De Jong D, Elghetany MT, Takahashi E, Emile JF, Ferry J, Fogelstrand L, Fontenay M, Germing U, Gujral S, Haferlach T, Harrison C, Hodge JC, Hu S, Jansen JH, Kanagal-Shamanna R, Kantarjian HM, Kratz CP, Li XQ, Lim MS, Loeb K, Loghavi S, Marcogliese A, Meshinchi S, Michaels P, Naresh KN, Natkunam Y, Nejati R, Ott G, Padron E, Patel KP, Patkar N, Picarsic J, Platzbecker U, Roberts I, Schuh A, Sewell W, Siebert R, Tembhare P, Tyner J, Verstovsek S, Wang W, Wood B, Xiao W, Yeung C, Hochhaus A (2022) The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia 36 (7):1703–1719. https://doi.org/10.1038/s41375-022-01613-1

  9. Larsson CA, Cote G, Quintas-Cardama A (2013) The changing mutational landscape of acute myeloid leukemia and myelodysplastic syndrome. Mol Cancer Res 11(8):815–827. https://doi.org/10.1158/1541-7786.MCR-12-0695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lindsley RC, Mar BG, Mazzola E, Grauman PV, Shareef S, Allen SL, Pigneux A, Wetzler M, Stuart RK, Erba HP, Damon LE, Powell BL, Lindeman N, Steensma DP, Wadleigh M, DeAngelo DJ, Neuberg D, Stone RM, Ebert BL (2015) Acute myeloid leukemia ontogeny is defined by distinct somatic mutations. Blood 125(9):1367–1376. https://doi.org/10.1182/blood-2014-11-610543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Lowenberg B, Bloomfield CD (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447. https://doi.org/10.1182/blood-2016-08-733196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hulegardh E, Nilsson C, Lazarevic V, Garelius H, Antunovic P, Rangert Derolf A, Mollgard L, Uggla B, Wennstrom L, Wahlin A, Hoglund M, Juliusson G, Stockelberg D, Lehmann S (2015) Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish Acute Leukemia Registry. Am J Hematol 90(3):208–214. https://doi.org/10.1002/ajh.23908

    Article  PubMed  Google Scholar 

  13. Fang H, He R, Chiu A, Viswanatha DS, Ketterling RP, Patnaik MS, Reichard KK (2020) Genetic factors in acute myeloid leukemia with myelodysplasia-related changes. Am J Clin Pathol 153(5):656–663. https://doi.org/10.1093/ajcp/aqz206

    Article  CAS  PubMed  Google Scholar 

  14. Montalban-Bravo G, Kanagal-Shamanna R, Class CA, Sasaki K, Ravandi F, Cortes JE, Daver N, Takahashi K, Short NJ, DiNardo CD, Jabbour E, Borthakur G, Naqvi K, Issa GC, Konopleva M, Khoury JD, Routbort M, Pierce S, Do KA, Bueso-Ramos C, Patel K, Kantarjian H, Garcia-Manero G, Kadia TM (2020) Outcomes of acute myeloid leukemia with myelodysplasia related changes depend on diagnostic criteria and therapy. Am J Hematol 95(6):612–622. https://doi.org/10.1002/ajh.25769

    Article  CAS  PubMed  Google Scholar 

  15. Seymour JF, Dohner H, Butrym A, Wierzbowska A, Selleslag D, Jang JH, Kumar R, Cavenagh J, Schuh AC, Candoni A, Recher C, Sandhu I, Del Castillo TB, Al-Ali HK, Falantes J, Stone RM, Minden MD, Weaver J, Songer S, Beach CL, Dombret H (2017) Azacitidine improves clinical outcomes in older patients with acute myeloid leukaemia with myelodysplasia-related changes compared with conventional care regimens. BMC Cancer 17(1):852. https://doi.org/10.1186/s12885-017-3803-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gao Y, Jia M, Mao Y, Cai H, Jiang X, Cao X, Zhou D, Li J (2022) Distinct mutation landscapes between acute myeloid leukemia with myelodysplasia-related changes and de novo acute myeloid leukemia. Am J Clin Pathol 157(5):691–700. https://doi.org/10.1093/ajcp/aqab172

    Article  CAS  PubMed  Google Scholar 

  17. Fuhrmann I, Lenk M, Haferlach T, Stengel A, Hutter S, Baer C, Meggendorfer M, Kern W, Haferlach C (2022) AML, NOS and AML-MRC as defined by multilineage dysplasia share a common mutation pattern which is distinct from AML-MRC as defined by MDS-related cytogenetics. Leukemia 36(7):1939–1942. https://doi.org/10.1038/s41375-022-01631-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Schnittger S, Bacher U, Haferlach C, Alpermann T, Dicker F, Sundermann J, Kern W, Haferlach T (2011) Characterization of NPM1-mutated AML with a history of myelodysplastic syndromes or myeloproliferative neoplasms. Leukemia 25(4):615–621. https://doi.org/10.1038/leu.2010.299

    Article  CAS  PubMed  Google Scholar 

  19. McKerrell T, Park N, Moreno T, Grove CS, Ponstingl H, Stephens J, Understanding Society Scientific G, Crawley C, Craig J, Scott MA, Hodkinson C, Baxter J, Rad R, Forsyth DR, Quail MA, Zeggini E, Ouwehand W, Varela I, Vassiliou GS (2015) Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Rep 10(8):1239–1245. https://doi.org/10.1016/j.celrep.2015.02.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Potter N, Miraki-Moud F, Ermini L, Titley I, Vijayaraghavan G, Papaemmanuil E, Campbell P, Gribben J, Taussig D, Greaves M (2019) Single cell analysis of clonal architecture in acute myeloid leukaemia. Leukemia 33(5):1113–1123. https://doi.org/10.1038/s41375-018-0319-2

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the research grant of the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number 2020R1G1A1004157).

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Authors and Affiliations

  1. Laboratory Medicine, Chungbuk National University College of Medicine, Cheongju, Chungcheongbuk-do, Republic of Korea

    Hee Sue Park & Bo Ra Son

  2. Laboratory Medicine, Chungbuk National University Hospital, Cheongju, Chungcheongbuk-do, Republic of Korea

    Hee Sue Park & Bo Ra Son

  3. Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Chungcheongbuk-do, Republic of Korea

    Hee Kyung Kim, Hong-sik Kim, Yaewon Yang, Hye Sook Han, Ki Hyeong Lee & Jihyun Kwon

  4. Internal Medicine, Chungbuk National University Hospital, Cheongju, Chungcheongbuk-do, Republic of Korea

    Hee Kyung Kim, Hong-sik Kim, Yaewon Yang, Hye Sook Han, Ki Hyeong Lee & Jihyun Kwon

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  1. Hee Sue Park
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Contributions

Conceptualization: HS Park and J Kwon; methodology: HS Park, BR Son, and J Kwon; investigation: HS Park, HK Kim, HS Kim, Y Yang, and J Kwon; formal analysis: HS Park and J Kwon; writing — original draft preparation: HS Park and J Kwon; writing — review and editing: HK Kim, HS Kim, Y Yang, HS Han, BR Son and KH Lee; funding acquisition: J Kwon; supervision: BR Son, HS Han, KH Lee, and J Kwon.

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Correspondence to Jihyun Kwon.

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Ethics statement

This study was approved by the Institutional Review Board of Chungbuk National University (CBNU-2018–05-006–001). All samples and data were obtained with informed consent, following institutional review board-approved protocols, and in accordance with the Declaration of Helsinki.

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Informed consent was obtained from all individuals participating in the study.

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The authors declare no competing interests.

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Park, H.S., Kim, H.K., Kim, Hs. et al. The new diagnostic criteria for myelodysplasia-related acute myeloid leukemia is useful for predicting clinical outcome: comparison of the 4th and 5th World Health Organization classifications. Ann Hematol 101, 2645–2654 (2022). https://doi.org/10.1007/s00277-022-05002-7

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