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Int. J. Mol. Sci. 2017, 18(8), 1618; doi:10.3390/ijms18081618

Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia

1
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
*
Author to whom correspondence should be addressed.
Received: 21 June 2017 / Revised: 11 July 2017 / Accepted: 14 July 2017 / Published: 26 July 2017
(This article belongs to the Special Issue The Biology and Treatment of Myeloid Leukaemias)
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Abstract

(1) Runt-related transcription factor 1 (RUNX1) mutations in acute myeloid leukemia (AML) are often associated with worse prognosis. We assessed co-occurring mutations, response to therapy, and clinical outcomes in patients with and without mutant RUNX1 (mRUNX1); (2) We analyzed 328 AML patients, including 177 patients younger than 65 years who received intensive chemotherapy and 151 patients >65 years who received hypomethylating agents. RUNX1 and co-existing mutations were identified using next-generation sequencing; (3) RUNX1 mutations were identified in 5.1% of younger patients and 15.9% of older patients, and were significantly associated with increasing age (p = 0.01) as well as intermediate-risk cytogenetics including normal karyotype (p = 0.02) in the elderly cohort, and with lower lactate dehydrogenase (LDH; p = 0.02) and higher platelet count (p = 0.012) overall. Identified co-occurring mutations were primarily ASXL1 mutations in older patients and RAS mutations in younger patients; FLT3-ITD and IDH1/2 co-mutations were also frequent. Younger mRUNX1 AML patients treated with intensive chemotherapy experienced inferior treatment outcomes. In older patients with AML treated with hypomethylating agent (HMA) therapy, response and survival was independent of RUNX1 status. Older mRUNX1 patients with prior myelodysplastic syndrome or myeloproliferative neoplasms (MDS/MPN) had particularly dismal outcome. Future studies should focus on the prognostic implications of RUNX1 mutations relative to other co-occurring mutations, and the potential role of hypomethylating agents for this molecularly-defined group. View Full-Text
Keywords: RUNX1; mutations; acute myeloid leukemia; hypomethylating agents; chemotherapy; prognosis RUNX1; mutations; acute myeloid leukemia; hypomethylating agents; chemotherapy; prognosis
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Khan, M.; Cortes, J.; Kadia, T.; Naqvi, K.; Brandt, M.; Pierce, S.; Patel, K.P.; Borthakur, G.; Ravandi, F.; Konopleva, M.; Kornblau, S.; Kantarjian, H.; Bhalla, K.; DiNardo, C.D. Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia. Int. J. Mol. Sci. 2017, 18, 1618.

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