Cargando…
Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia
(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, in...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578010/ https://www.ncbi.nlm.nih.gov/pubmed/28933735 http://dx.doi.org/10.3390/ijms18081618 |
_version_ | 1783260447802130432 |
---|---|
author | Khan, Maliha Cortes, Jorge Kadia, Tapan Naqvi, Kiran Brandt, Mark Pierce, Sherry Patel, Keyur P. Borthakur, Gautam Ravandi, Farhad Konopleva, Marina Kornblau, Steven Kantarjian, Hagop Bhalla, Kapil DiNardo, Courtney D. |
author_facet | Khan, Maliha Cortes, Jorge Kadia, Tapan Naqvi, Kiran Brandt, Mark Pierce, Sherry Patel, Keyur P. Borthakur, Gautam Ravandi, Farhad Konopleva, Marina Kornblau, Steven Kantarjian, Hagop Bhalla, Kapil DiNardo, Courtney D. |
author_sort | Khan, Maliha |
collection | PubMed |
description | (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. |
format | Online Article Text |
id | pubmed-5578010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-55780102017-09-05 Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia Khan, Maliha Cortes, Jorge Kadia, Tapan Naqvi, Kiran Brandt, Mark Pierce, Sherry Patel, Keyur P. Borthakur, Gautam Ravandi, Farhad Konopleva, Marina Kornblau, Steven Kantarjian, Hagop Bhalla, Kapil DiNardo, Courtney D. Int J Mol Sci Article (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. MDPI 2017-07-26 /pmc/articles/PMC5578010/ /pubmed/28933735 http://dx.doi.org/10.3390/ijms18081618 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Khan, Maliha Cortes, Jorge Kadia, Tapan Naqvi, Kiran Brandt, Mark Pierce, Sherry Patel, Keyur P. Borthakur, Gautam Ravandi, Farhad Konopleva, Marina Kornblau, Steven Kantarjian, Hagop Bhalla, Kapil DiNardo, Courtney D. Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia |
title | Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia |
title_full | Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia |
title_fullStr | Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia |
title_full_unstemmed | Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia |
title_short | Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia |
title_sort | clinical outcomes and co-occurring mutations in patients with runx1-mutated acute myeloid leukemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578010/ https://www.ncbi.nlm.nih.gov/pubmed/28933735 http://dx.doi.org/10.3390/ijms18081618 |
work_keys_str_mv | AT khanmaliha clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT cortesjorge clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT kadiatapan clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT naqvikiran clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT brandtmark clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT piercesherry clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT patelkeyurp clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT borthakurgautam clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT ravandifarhad clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT konoplevamarina clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT kornblausteven clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT kantarjianhagop clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT bhallakapil clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia AT dinardocourtneyd clinicaloutcomesandcooccurringmutationsinpatientswithrunx1mutatedacutemyeloidleukemia |