Synapse - Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia

Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia Journal Article

Authors:	McCarter, J. G. W.; Nemirovsky, D.; Famulare, C. A.; Farnoud, N.; Mohanty, A. S.; Stone-Molloy, Z. S.; Chervin, J.; Ball, B. J.; Epstein-Peterson, Z. D.; Arcila, M. E.; Stonestrom, A. J.; Dunbar, A.; Cai, S. F.; Glass, J. L.; Geyer, M. B.; Rampal, R. K.; Berman, E.; Abdel-Wahab, O. I.; Stein, E. M.; Tallman, M. S.; Levine, R. L.; Goldberg, A. D.; Papaemmanuil, E.; Zhang, Y.; Roshal, M.; Derkach, A.; Xiao, W.
Article Title:	Interaction between myelodysplasia-related gene mutations and ontogeny in acute myeloid leukemia
Abstract:	Accurate classification and risk stratification are critical for clinical decision making in patients with acute myeloid leukemia (AML). In the newly proposed World Health Organization and International Consensus classifications of hematolymphoid neoplasms, the presence of myelodysplasia-related (MR) gene mutations is included as 1 of the diagnostic criteria for AML, AML-MR, based largely on the assumption that these mutations are specific for AML with an antecedent myelodysplastic syndrome. ICC also prioritizes MR gene mutations over ontogeny (as defined in the clinical history). Furthermore, European LeukemiaNet (ELN) 2022 stratifies these MR gene mutations into the adverse-risk group. By thoroughly annotating a cohort of 344 newly diagnosed patients with AML treated at the Memorial Sloan Kettering Cancer Center, we show that ontogeny assignments based on the database registry lack accuracy. MR gene mutations are frequently observed in de novo AML. Among the MR gene mutations, only EZH2 and SF3B1 were associated with an inferior outcome in the univariate analysis. In a multivariate analysis, AML ontogeny had independent prognostic values even after adjusting for age, treatment, allo-transplant and genomic classes or ELN risks. Ontogeny also helped stratify the outcome of AML with MR gene mutations. Finally, de novo AML with MR gene mutations did not show an adverse outcome. In summary, our study emphasizes the importance of accurate ontogeny designation in clinical studies, demonstrates the independent prognostic value of AML ontogeny, and questions the current classification and risk stratification of AML with MR gene mutations.
Keywords:	neoplasms; classification; dysplasia; world-health-organization; revision
Journal Title:	Blood Advances
Volume:	7
Issue:	17
ISSN:	2473-9529
Publisher:	American Society of Hematology
Date Published:	2023-09-12
Start Page:	5000
End Page:	5013
Language:	English
ACCESSION:	WOS:001068387000001
DOI:	10.1182/bloodadvances.2023009675
PROVIDER:	wos
PMCID:	PMC10471939
PUBMED:	37142255
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Wenbin Xiao -- Source: Wos