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Review
. 2024 Jan 12:13:1329298.
doi: 10.3389/fonc.2023.1329298. eCollection 2023.

Co-occurrence of JAK2-V617 F mutation and BCR::ABL1 translocation in chronic myeloproliferative neoplasms: a potentially confounding genetic combination

Magda Zanelli  1 , Alessandra Bisagni  1 , Francesca Sanguedolce  2 , Giuseppe Broggi  3 , Valentina Fragliasso  4 , Maurizio Zizzo  5 , Andrea Palicelli  1 , Giovanni Martino  6   7 , Camilla Cresta  6 , Cecilia Caprera  6 , Matteo Corsi  6 , Pietro Gentile  8 , Fabrizio Gozzi  8 , Domenico Trombetta  9 , Paola Parente  9 , Rosario Caltabiano  3 , Nektarios Koufopoulos  10 , Luca Cimino  8   11 , Alberto Cavazza  1 , Giulio Fraternali Orcioni  12 , Stefano Ascani  6
Affiliations
Review

Co-occurrence of JAK2-V617 F mutation and BCR::ABL1 translocation in chronic myeloproliferative neoplasms: a potentially confounding genetic combination

Magda Zanelli et al. Front Oncol. .

Abstract

Myeloproliferative neoplasms (MPNs) are classified into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) and Ph-negative MPNs. BCR::ABL1 translocation is the key genetic event of CML, whereas JAK2/MPL/CALR mutations are molecular aberrations of Ph-negative MPNs. Despite initially considered mutually exclusive genetic aberrations, the co-occurrence of BCR::ABL1 and JAK2 has been reported in a limited number of cases. The two genetic alterations may be identified either at the same time or JAK2 aberration may be detected in patients with a previous CML treated with tyrosine kinase inhibitors or, finally, BCR::ABL1 translocation occurs in patients with a history of JAK2-positive MPN. This combination of genomic alterations is potentially confounding with clinical manifestations often misinterpreted either as disease progression or drug resistance, therefore leading to inappropriate patient's treatment. Our systematic review aims to improve hematologist and pathologist knowledge on this rare subset of patients. Starting from the presentation of two additional cases from our routine daily practice, we focus mainly on clinical, laboratory, and bone marrow histological findings, which may represent useful clues of BCR::ABL1 and JAK2 co-occurrence. The interaction between JAK2 and BCR::ABL1 clones during the disease course as well as therapy and outcome are presented.

Keywords: BCR::ABL1; JAK2; chronic myeloid leukemia; essential thrombocythemia; myeloproliferative neoplasm; polycythemia vera; primary myelofibrosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Medium power view of BM biopsy showing hypercellular marrow with normal-maturing prevalent granulopoiesis and clusters of variably sized MKs including large forms with bulbous nuclei (Hematoxylin and eosin, 200x magnification).
Figure 2
Figure 2
High power view of BM highlighting a dense cluster of variably-sized MKs (Hematoxylin and eosin, 400× magnification).
Figure 3
Figure 3
Medium power view of BM biopsy showing hypercellularity with high myeloid: erythroid ratio and mainly small MKs with scarce tendency to form clusters (Hematoxylin and eosin, 200× magnification).
Figure 4
Figure 4
PRISMA flow chart of literature search.
Figure 5
Figure 5
Graphic showing the frequency of cases with opposite growth of BCR::ABL1 and JAK2 clones under TKI treatment in the three different groups of patients.
See this image and copyright information in PMC

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References

    1. WHO Classification of Tumours Editorial Board . WHO Classification of Tumours Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC; (2017).
    1. Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. . The 5th edition of the world health organization classification of haematolymphoid tumours: myeloid and histiocytic/ dendritic neoplasms. Leukemia (2022) 36:1703–19. doi: 10.1038/s41375-022-01613-1 - DOI - PMC - PubMed
    1. Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka HM, et al. . International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood (2022) 140:1200–28. doi: 10.1182/blood.2022015850 - DOI - PMC - PubMed
    1. Kramer A, Reiter A, Kruth J, Erben P, Hochhaus A, Muller M, et al. . JAK2-V617F mutation in a patient with Philadelphia-chromosome-positive chronic myeloid leukemia. Lancet Oncol (2007) 8:658–60. doi: 10.1016/S1470-2045(07)70206-1 - DOI - PubMed
    1. Inami M, Inokuchi K, Okabe M, Kosaka F, Mitamura Y, Yamaguchi H. Polycythemia associate with the JAK2V617F mutation emerged during treatment of chronic myelogenous leukemia. Leukemia (2007) 21:1103–4. doi: 10.1038/sj.leu.2404591 - DOI - PubMed