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. 2025 Aug 12;9(15):3814-3818.
doi: 10.1182/bloodadvances.2025016374.

RAS mutation identifies a poor prognostic molecular subtype of therapy-related myeloid neoplasm

Chung Hoow Kok  1   2   3 , Aref Al-Kali  4 , Daniel Thomas  2   5   6 , Rong He  4 , Monika M Kutyna  2   5   6 , Hassan Alkhateeb  4 , Kelly Lim  2   6 , Antoine N Saliba  4 , Carla Toop  5 , Aasiya Matin  4 , Hamish Scott  1   3 , Naseema Gangat  4 , Anna Brown  1   3 , Abhishek Mangaonkar  4 , Christopher N Hahn  1   3 , Kebede Begna  4 , Kevin Hung  2   5 , Patricia Greipp  7 , William J Hogan  4 , Mrinal Patnaik  4 , Mithun Shah  4 , Devendra K Hiwase  2   3   5   6
Affiliations

RAS mutation identifies a poor prognostic molecular subtype of therapy-related myeloid neoplasm

Chung Hoow Kok et al. Blood Adv. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: M.S. received research funding for the institution from Astellas, AbbVie, Celgene, Kura Oncology, and Marker Therapeutics. D.K.H. is a member of the board of directors or advisory committees of AbbVie and Novartis. N.G. served on the advisory board for Agios and Disc Medicine. P.G. served on an advisory board for AbbVie. A.N.S. received research funding for the institution from Kura Oncology and Chordia Therapeutics. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
RASmut were more prevalent in TP53wt and are enriched in KMT2A-r. (A) RASmut were highly prevalent in TP53wt compared with TP53mut t-MNs; (B-C) most prevalent mutational hot spots (G12, G13, and Q61) in NRASmut and KRASmut (G12, G13, and Q61); (D) volcano plot comparing clinical, cytogenetic, and mutational profiles between TP53mut and RASmut. Poor-risk cytogenetics were enriched in TP53mut, whereas KMT2A-r and other somatic mutations are more frequent in RASmut t-MN; (E) complex karyotype (CK) was highly prevalent in TP53mut but not in RASmut t-MN; (F) KMT2A-r was enriched in RASmut cases compared to TP53mut and RASwt t-MN; and (G) t(9;11) was highly prevalent in KRASmut compared to NRASmut.
Figure 2.
Figure 2.
RASmut is enriched in t-AML and is associated with poor prognosis. (A) t-AML was more prevalent in RASmut than RASwt t-MN. (B) t-AML was especially more prevalent in the presence of KMT2A-r. (C) Substitutions at amino acid position 13 (G13D/C) were highly enriched in t-AML. In contrast, mutations at position 12 (G12D/V/C) were more frequently associated with t-MDS. (D) RASmut was associated with survival comparable to TP53-mutated t-MN, (E) t-MDS, and (F) t-AML. (G) Multivariable Cox proportional hazard analysis demonstrated that RASmut was associated with poor survival independent of allo-SCT, t-MN phenotype, and CKs. (H) NRASmut was associated with significantly poorer OS than KRASmut t-AML. Allo-SCT, allogeneic stem cell transplant; OS, overall survival.
See this image and copyright information in PMC

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