KRAS Mutations Predict Inferior Post-Remission Outcomes in Newly Diagnosed Acute Myeloid Leukemia With MAPK Pathway Mutations

Kensuke Takaoka; Sarah Mott; Ratdanai Yodsuwan; Sakditad Saowapa; Manasawee Tanariyakul; Chalothorn Wannaphut; Kittika Poonsombudlert

doi:10.1111/ejh.70270

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KRAS Mutations Predict Inferior Post-Remission Outcomes in Newly Diagnosed Acute Myeloid Leukemia With MAPK Pathway Mutations

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KRAS Mutations Predict Inferior Post-Remission Outcomes in Newly Diagnosed Acute Myeloid Leukemia With MAPK Pathway Mutations

Kensuke Takaoka, Sarah Mott, Ratdanai Yodsuwan, Sakditad Saowapa, Manasawee Tanariyakul, Chalothorn Wannaphut and Kittika Poonsombudlert

European journal of haematology

07/24/2026

DOI: 10.1111/ejh.70270

PMID: 42498507

Appears in UI Libraries Support Open Access

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Abstract

Somatic mutations in the MAPK signaling pathway are frequently identified at AML diagnosis; however, their impact on treatment resistance and long-term survival remains unclear. We conducted a retrospective study of patients with newly diagnosed MAPK-mutated AML seen at the University of Iowa Health Care. The endpoints were overall survival (OS), composite complete remission (CRc) following induction therapy, and relapse-free survival (RFS). Logistic and Cox regression models were used. Seventy-four patients were included and 62 were induction eligible. Of the 62 patients receiving treatment, intensive induction was administered in 52.7%. The estimated 5-year OS was 28.9%. On multivariable analysis, European LeukemiaNet 2022 adverse risk (hazard ratio [HR]: 3.56, 95% confident interval [CI]: 1.52-8.32) and KRAS mutation (HR: 2.14, 95% CI: 1.10-4.17) conferred inferior OS. Abnormal karyotype (odds ratio [OR]: 0.25, 95% CI: 0.07-0.89) and increasing age (OR: 0.97, 95% CI: 0.94-0.99) were associated with decreased odds of achieving a CRc. The median RFS after achieving a CRc was 13.3 months. We found that KRAS mutation conferred an inferior effect on OS and RFS but not CRc. These findings suggest that KRAS mutations may confer adverse prognostic significance and warrant validation in larger, multicenter cohorts.

AML

NRAS

CRc

KRAS

MAPK

HSCT

RFS

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Details

Title: Subtitle: KRAS Mutations Predict Inferior Post-Remission Outcomes in Newly Diagnosed Acute Myeloid Leukemia With MAPK Pathway Mutations
Creators: Kensuke Takaoka - University of Iowa
Sarah Mott - University of Iowa
Ratdanai Yodsuwan - University of Iowa
Sakditad Saowapa - University of Iowa
Manasawee Tanariyakul - University of Iowa
Chalothorn Wannaphut - University of Hawaiʻi at Mānoa
Kittika Poonsombudlert - University of Iowa
Resource Type: Journal article
Publication Details: European journal of haematology
DOI: 10.1111/ejh.70270
PMID: 42498507
NLM abbreviation: Eur J Haematol
ISSN: 1600-0609
eISSN: 1600-0609
Publisher: Wiley
Language: English
Electronic publication date: 07/24/2026
Academic Unit: Internal Medicine
Record Identifier: 9985183561502771

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