Pediatric non-Down syndrome acute megakaryoblastic leukemia with  GATA1  mutations

M. V. Gaskova; Гаськова М. В.; Yu. V. Olshanskaya; Ольшанская Ю. В.; Z. A. Abashidze; Абашидзе З. А.; E. A. Zerkalenkova; Зеркаленкова Е. А.; I. I. Kalinina; Калинина И. И.; D. А. Venyov; Венев Д. А.; O. I. Soldatkina; Солдаткина О. И.; A. N. Kazakova; Казакова А. Н.; L. A. Khachatryan; Хачатрян Л. А.; K. A. Voronin; Воронин К. А.; M. E. Dubrovina; Дубровина М. Э.; S. A. Plyasunova; Плясунова С. А.; A. A. Semchenkova; Семченкова А. А.; S. A. Kashpor; Кашпор С. А.; E. V. Mikhailova; Михайлова Е. В.; A. M. Popov; Попов А. М.; M. A. Maschan; Масчан М. А.; G. A. Novichkova; Новичкова Г. А.; A. A. Maschan; Масчан А. А.

doi:10.24287/1726-1708-2025-24-1-50-57

Pediatric non-Down syndrome acute megakaryoblastic leukemia with GATA1 mutations

Authors: Gaskova M.V.¹, Olshanskaya Y.V.¹, Abashidze Z.A.¹, Zerkalenkova E.A.¹, Kalinina I.I.¹, Venyov D.А.¹, Soldatkina O.I.¹, Kazakova A.N.¹, Khachatryan L.A.¹, Voronin K.A.¹, Dubrovina M.E.¹, Plyasunova S.A.¹, Semchenkova A.A.¹, Kashpor S.A.¹, Mikhailova E.V.¹, Popov A.M.¹, Maschan M.A.¹, Novichkova G.A.¹, Maschan A.A.¹
Affiliations:
1. The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation
Issue: Vol 24, No 1 (2025)
Pages: 50-57
Section: ORIGINAL ARTICLES
Submitted: 31.01.2025
Accepted: 25.02.2025
Published: 08.07.2025
URL: https://hemoncim.com/jour/article/view/957
DOI: https://doi.org/10.24287/1726-1708-2025-24-1-50-57
ID: 957

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Abstract

Acute megakaryoblastic leukemia (AMKL) accounts for 4–15% of childhood acute myeloid leukemia and most often affects children with Down syndrome (DS). AMKL with DS (DS-AMKL) is characterized by mutations in the GATA1 gene, the absence of recurrent translocations and high sensitivity to multi-agent chemotherapy. In children without DS, AMKL demonstrates high genetic diversity: for example, such patients can have a variant that is biologically and clinically similar to DS-AMKL and is also characterized by mutations in the GATA1 gene and the absence of known fusion transcripts. Trisomy 21 is somatic, i.e. it can be detected only in leukemic cells. This is the so-called DS-like AMKL. To better characterize DS-like AMKL, we analyzed clinical and hematological characteristics, genetic profiles, and response to therapy in 65 patients with AMKL without phenotypic features of DS. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. A mutation in the GATA1 gene was detected in 14 (21%) patients. All 14 patients had confirmed somatic trisomy 21 in blast cells. In these cases, blast cells had a profile of additional mutations and chromosomal abnormalities that was similar to DS-AMKL. Survival rates in the cohort of interest were significantly higher than in the patients without GATA1 mutations. Thus, all patients with AMKL should be tested for mutations in the GATA1 gene to more accurately predict their response to therapy.