Late acquisition of BCR::ABL1 during clonal evolution of SAMD9-associated MDS with phenotypic shift from AML to B-ALL.

Authors

Yusuke Nakata, Anna Hiratsuka, Takeshi Yoroidaka, Wakana Takahashi, Itaru Nishikawa, Masataka Sakashita, Shinya Yamada, Hiroki Mizumaki, Akiyo Yoshida, Tatsuya Imi, Hiroyuki Maruyama, Hiroyuki Takamatsu, Kohei Hosokawa, Yasuhito Nannya, Seishi Ogawa, Toshihiro Miyamoto

Published in

International journal of hematology. Jul 30, 2026. Epub Jul 30, 2026.

Abstract

We describe a unique case of SAMD9-associated myelodysplastic syndrome (MDS) with monosomy 7 that evolved over 16 years into BCR::ABL1-positive acute myeloid leukemia (AML) and subsequently manifested as B-cell acute lymphoblastic leukemia (B-ALL). Genomic analysis at AML diagnosis revealed a germline SAMD9 mutation together with somatic RUNX1 and PPM1D mutations, supporting stepwise clonal evolution, with BCR::ABL1 emerging as a late leukemogenic event. The dominant leukemic population at AML onset showed myeloid morphology and immunophenotype, whereas a minor CD19⁺CD10⁺ population was already detectable. Following venetoclax and azacitidine therapy, the dominant leukemic phenotype shifted to B-ALL while retaining BCR::ABL1 positivity. Detection of the Philadelphia chromosome in mature neutrophils at both AML onset and ALL relapse supported multilineage involvement of a multipotent BCR::ABL1-positive clone. Ponatinib achieved disease control. This case highlights late acquisition of BCR::ABL1 during SAMD9-associated clonal evolution and therapy-driven phenotypic shift within a shared Ph-positive leukemic stem-cell hierarchy.

PMID:
42533241
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.

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