Concomitant presence of JAK2V617F mutation and BCR‑ABL translocation in two patients: A new entity or a variant of myeloproliferative neoplasms (Case report)

Abstract

Myeloproliferative neoplasms (MPNs) are classically divided into BCR RhoGEF and GTPase activating protein (BCR)-ABL proto‑oncogene 1 non‑receptor tyrosine kinase (ABL) positive chronic myeloid leukemia (CML) and BCR‑ABL negative MPNs, including essential thrombocythemia (ET). One of the major diagnostic criteria for ET is the absence of the philadelphia chromosome, thus when present it is almost indicative of CML. ET and CML are considered to be mutually exclusive; however, there are rare situations in which patients with ET present positive BCR‑ABL without the features of CML. Although from the literature review, the frequency of JAK2V617F mutation and BCR‑ABL translocation coexistence in MPNs is low, it may be higher than expected. The current study reported cases of two patients with an initial diagnosis of ET in the presence of JAK2V617F mutation and BCR‑ABL translocation by fluorescent in situ hybridization. Both patients presented with a heterozygous BCR‑ABL translocation, and absence of p190 and p210 transcripts, seemingly a der(9) in the background of an ET JAK2V617F mutation.

Non-receptor Tyrosine Kinases Role and Significance in Hematological Malignancies

“…Some reports have also suggested JAK2 V617F clonal involvement of B [143,144], T [143], and NK lymphocytes [83], also confirming the stem cell nature of JAK2 V617F MPNs [102]. Lower frequencies of V617F mutation occur in PN-CML, chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, and rare cases of AML (megakaryocytic and in combination with other well-defined genetic abnormalities, such as BCR-ABL1) [145]. There is also evidence of association with certain solid tumors (generally non-hematological types) [51,114,117,[146][147][148].…”

A 68-Year-Old Man with a Cytogenetic Diagnosis of Chronic Myeloid Leukemia and Bone Marrow Findings of Philadelphia Chromosome Translocation Between the Long Arm of Chromosomes 9 and 22, Leading to the BCR-ABL1 Fusion Gene and V617F Mutation in the JAK2 Gene

“…JAK2 mutations are present in up to 95% of PV cases and 65% of ET and PMF cases [5]. BCR-ABL1 and JAK2 mutations are thought to be mutually exclusive, but recent data and case reports have described cases in which these mutations occur concomitantly [6][7][8][9][10][11][12][13]. In this report, we describe a unique coincidence presentation of CML and JAK2-positive thrombocytosis one month after initiating tyrosine kinase inhibitor (TKI) therapy.…”