Faculty Collaboration Database

JAK2 V617F mutation and associated chromosomal alterations in primary and secondary myelofibrosis and post-HCT outcomes. Blood Adv 2023 Dec 26;7(24):7506-7515

Date

11/27/2023

Pubmed ID

38011490

Pubmed Central ID

PMC10758737

DOI

10.1182/bloodadvances.2023010882

Scopus ID

2-s2.0-85181717421 (requires institutional sign-in at Scopus site)

Abstract

JAK2 V617F is the most common driver mutation in primary or secondary myelofibrosis for which allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment. Knowledge of the prognostic utility of JAK2 alterations in the HCT setting is limited. We identified all patients with MF who received HCT between 2000 and 2016 and had a pre-HCT blood sample (N = 973) available at the Center of International Blood and Marrow Transplant Research biorepository. PacBio sequencing and single nucleotide polymorphism-array genotyping were used to identify JAK2V617F mutation and associated mosaic chromosomal alterations (mCAs), respectively. Cox proportional hazard models were used for HCT outcome analyses. Genomic testing was complete for 924 patients with MF (634 primary MF [PMF], 135 postpolycythemia vera [PPV-MF], and 155 postessential thrombocytopenia [PET-MF]). JAK2V617F affected 562 patients (57.6% of PMF, 97% of PPV-MF, and 42.6% of PET-MF). Almost all patients with mCAs involving the JAK2 region (97.9%) were JAK2V617-positive. In PMF, JAK2V617F mutation status, allele burden, or identified mCAs were not associated with disease progression/relapse, nonrelapse mortality (NRM), or overall survival. Almost all PPV-MF were JAK2V617F-positive (97%), with no association between HCT outcomes and mutation allele burden or mCAs. In PET-MF, JAK2V617F high mutation allele burden (≥60%) was associated with excess risk of NRM, restricted to transplants received in the era of JAK inhibitors (2013-2016; hazard ratio = 7.65; 95% confidence interval = 2.10-27.82; P = .002). However, allele burden was not associated with post-HCT disease progression/relapse or survival. Our findings support the concept that HCT can mitigate the known negative effect of JAK2V617F in patients with MF, particularly for PMF and PPV-MF.

Author List

Rafati M, Brown DW, Zhou W, Jones K, Luo W, St Martin A, Wang Y, He M, Spellman SR, Wang T, Deeg HJ, Gupta V, Lee SJ, Bolon YT, Chanock SJ, Machiela MJ, Saber W, Gadalla SM

Authors

Wael Saber MD, MS Professor in the Medicine department at Medical College of Wisconsin
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Chromosome Aberrations
Disease Progression
Humans
Janus Kinase 2
Mutation
Primary Myelofibrosis
Prognosis
Recurrence