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Poor Survival and Differential Impact of Genetic Features of Black Patients with Acute Myeloid Leukemia.

ABSTRACT: Clinical outcome of patients with acute myeloid leukemia (AML) is associated with cytogenetic and molecular factors and patient demographics (e.g., age and race). We compared survival of 25,523 non-Hispanic Black and White adults with AML using Surveillance Epidemiology and End Results (SEER) Program data and performed mutational profiling of 1,339 patients with AML treated on frontline Alliance for Clinical Trials in Oncology (Alliance) protocols. Black patients had shorter survival than White patients, both in SEER and in the setting of Alliance clinical trials. The disparity was especially pronounced in Black patients <60 years, after adjustment for socioeconomic (SEER) and molecular (Alliance) factors. Black race was an independent prognosticator of poor survival. Gene mutation profiles showed fewer NPM1 and more IDH2 mutations in younger Black patients. Overall survival of younger Black patients was adversely affected by IDH2 mutations and FLT3-ITD, but, in contrast to White patients, was not improved by NPM1 mutations. SIGNIFICANCE: We show that young Black patients have not benefited as much as White patients from recent progress in AML treatment in the United States. Our data suggest that both socioeconomic factors and differences in disease biology contribute to the survival disparity and need to be urgently addressed.See related commentary by Vyas, p. 540.This article is highlighted in the In This Issue feature, p. 521.

SUBMITTER: Bhatnagar B

PROVIDER: S-EPMC7933110 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Poor Survival and Differential Impact of Genetic Features of Black Patients with Acute Myeloid Leukemia.

Bhatnagar Bhavana B Kohlschmidt Jessica J Mrózek Krzysztof K Zhao Qiuhong Q Fisher James L JL Nicolet Deedra D Walker Christopher J CJ Mims Alice S AS Oakes Christopher C Giacopelli Brian B Orwick Shelley S Boateng Isaiah I Blachly James S JS Maharry Sophia E SE Carroll Andrew J AJ Powell Bayard L BL Kolitz Jonathan E JE Stone Richard M RM Byrd John C JC Paskett Electra D ED de la Chapelle Albert A Garzon Ramiro R Eisfeld Ann-Kathrin AK

Cancer discovery 20201204 3

Clinical outcome of patients with acute myeloid leukemia (AML) is associated with cytogenetic and molecular factors and patient demographics (e.g., age and race). We compared survival of 25,523 non-Hispanic Black and White adults with AML using Surveillance Epidemiology and End Results (SEER) Program data and performed mutational profiling of 1,339 patients with AML treated on frontline Alliance for Clinical Trials in Oncology (Alliance) protocols. Black patients had shorter survival than White ...[more]

PMID: 33277314

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Project description:Background: Acute myeloid leukemia (AML) is a heterogeneous malignant disease. SLC25A1, the gene encoding mitochondrial carrier subfamily of solute carrier proteins, was reported to be overexpressed in certain solid tumors. However, its expression and value as prognostic marker has not been assessed in AML. Methods: We retrieved RNA profile and corresponding clinical data of AML patients from the Beat AML, TCGA, and TARGET databases (TARGET_AML). Patients in the TCGA cohort were well-grouped into two group based on SLC25A1 and differentially expressed genes were determined between the SLC25A1 high and low group. The expression of SLC25A1 was validated with clinical samples. The survival and apoptosis of two AML cell lines were analyzed with SLC25A1 inhibitor (CTPI-2) treatment. Cox and the least absolute shrinkage and selection operator (LASSO) regression analyses were applied to Beat AML database to identify SLC25A1-associated genes for the construction of a prognostic risk-scoring model. Survival analysis was performed by Kaplan-Meier and receiver operator characteristic curves. Results: Our analysis revealed that high expressed level of SLC25A1 in AML patients correlates with unfavorable prognosis. Moreover, SLC25A1 expression was positively associated with metabolism activity. We further demonstrated that the inhibition of SLC25A1 could inhibit the proliferation and increase the apoptosis of AML cells. In addition, a panel of SLC25A1-associated genes, was identified to construct a prognostic risk-scoring model. This SLC25A1-associated prognostic signature (SPS) is an independent risk factor with high area under curve (AUC) values of receiver operating characteristic (ROC) curves. A high SPS in leukemia patients is associated with poor survival. A Prognostic nomogram including the SPS and other clinical parameters, was constructed and its predictive efficiency was confirmed. Conclusion: We have successfully established a SPS prognostic model that predict outcome and risk stratification in AML. This risk model can be used as an independent biomarker to assess prognosis of AML.

Dataset Information

Poor Survival and Differential Impact of Genetic Features of Black Patients with Acute Myeloid Leukemia.

Publications

Poor Survival and Differential Impact of Genetic Features of Black Patients with Acute Myeloid Leukemia.

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