<i>FLT3</i>-ITD Allelic Burden and Acute Promyelocytic Leukemia Risk Stratification

Andrew Y. Li; Sarah M. Kashanian; Bryan C. Hambley; Kyle Zacholski; Vu H. Duong; Firas El Chaer; Noa G. Holtzman; Ivana Gojo; Jonathan A. Webster; Kelly J. Norsworthy; Bruce Douglas Smith; Amy E. DeZern; Mark J. Levis; Maria R. Baer; Farin Kamangar; Gabriel Ghiaur; Ashkan Emadi

doi:10.3390/biology10030243

Biology (Mar 2021)

<i>FLT3</i>-ITD Allelic Burden and Acute Promyelocytic Leukemia Risk Stratification

Andrew Y. Li,
Sarah M. Kashanian,
Bryan C. Hambley,
Kyle Zacholski,
Vu H. Duong,
Firas El Chaer,
Noa G. Holtzman,
Ivana Gojo,
Jonathan A. Webster,
Kelly J. Norsworthy,
Bruce Douglas Smith,
Amy E. DeZern,
Mark J. Levis,
Maria R. Baer,
Farin Kamangar,
Gabriel Ghiaur,
Ashkan Emadi

Affiliations

Andrew Y. Li: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Sarah M. Kashanian: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Bryan C. Hambley: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Kyle Zacholski: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Vu H. Duong: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Firas El Chaer: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Noa G. Holtzman: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Ivana Gojo: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Jonathan A. Webster: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Kelly J. Norsworthy: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Bruce Douglas Smith: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Amy E. DeZern: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Mark J. Levis: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Maria R. Baer: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Farin Kamangar: Department of Biology, School of Computer, Mathematical, and Natural Sciences, Morgan State University, Baltimore, MD 21251, USA
Gabriel Ghiaur: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA
Ashkan Emadi: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA

DOI: https://doi.org/10.3390/biology10030243
Journal volume & issue: Vol. 10, no. 3
p. 243

Abstract

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The significance of FLT3-ITD in acute promyelocytic leukemia (APL) is not well-established. We performed a bi-center retrospective study of 138 APL patients, 59 (42.8%) of whom had FLT3-ITD. APL patients with FLT3-ITD had higher baseline white blood cell counts (WBCs) (p p = 0.03), higher aspartate aminotransferase (p = 0.001), lower platelets (p = 0.004), lower fibrinogen (p = 0.003), and higher incidences of disseminated intravascular coagulation (p = 0.005), M3v variant morphology (p p FLT3-ITD was associated with inferior post-consolidation complete remission (CR) (p = 0.02) and 5-year overall survival (OS) of 79.7%, compared to 94.4% for FLT3-WT (wild-type) (p = 0.02). FLT3-ITD was strongly associated with baseline WBCs ≥ 25 × 109/L (odds ratio (OR): 54.4; 95% CI: 10.4–286.1; p FLT3-ITD allelic burdens correlated with high-risk (HR) Sanz scores and high WBCs, with every 1% increase in allelic burden corresponding to a 0.6 × 109/L increase in WBC. HR APL was associated with a 38.5% increase in allelic burden compared with low-risk (LR) APL (95% CI: 19.8–57.2; p FLT3-ITD APL is a distinct subtype of APL that warrants further study to delineate potential differences in therapeutic approach.

Published in Biology

ISSN: 2079-7737 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.mdpi.com/journal/biology

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