CHIC2 DELETION-ASSOCIATED HYPEREOSINOPHILIA AND SUBSEQUENT JAK2 V617F POSITIVE THROMBOCYTOSIS

Abstract

Background and aim

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) are myeloid or lymphoid neoplasms driven by rearrangements involving genes encoding specific tyrosine kinases. These BCR::ABL1-negative diseases have long been recognized for their sensitivity to tyrosine kinase inhibitors. Herein, we present an interesting case diagnosed as myeloid neoplasm with abnormality of PDGFRA.

Case presentation

A 63-year-old female patient with known glaucoma, hypothyroidism, and vitiligo was admitted to our clinic 8-years ago with fatigue. The patient had splenomegaly and eosinophil-predominant (10 × 10⁹/L) leukocytosis (70.8 × 10⁹/L). Secondary causes of eosinophilia (rheumatologic, infectious and immunologic) were excluded. Although not directly attributed to the patient's hypereosinophilia, echocardiographic left ventricular contraction abnormality was observed. Bone marrow aspiration and biopsy were hypercellular and showed 35%‒40% eosinophils. With a preliminary diagnosis of hypereosinophilic syndrome, the patient was treated with steroids and then with hydroxyurea. Karyotype analysis was normal and FISH for t(9;22) was negative. The FISH panel revealed a 76% CHIC2 (4q12) deletion, but was negative for abnormalities of PDGFRB, FGFR1, and FIP1L1::PDGFRA fusion. The patient was switched to imatinib treatment. While the patient was followed in hematological remission for a long time with imatinib, thrombocytosis (807 × 10⁹/L) was detected in the patient six months ago. The patient had suppressed erythropoietin level (1.94 mu/mL) and JAK2 V617F mutation. Low-dose hydroxyurea was combined with imatinib. Hematological remission was regained.

Discussion

The majority of MLN-TK cases associated with PDGFRA rearrangements have cytogenetically cryptic deletion of 4q12 resulting in FIP1L1::PDGFRA. Although FIP1L1::PDGFRA fusion could not be demonstrated in this patient, it was thought that the patient had a myeloid neoplasm with abnormality of PDGFRA class due to CHIC2 deletion and typical clinical findings. The fact that the patient responded to treatment for many years seems to be evidence of this. The detection of JAK2 mutation during follow-up raised the question of whether this clone was present in the patient from the beginning or was acquired later.