Chronic Lymphocytic Leukemia and JAK2 V617F Positive Essential Thrombocythemia: Distinct Clonal Diseases?

Abstract

Turkish Abstract

Introduction

The coexistence of myeloproliferative neoplasia (MPN) and chronic lymphocytic leukemia (CLL) is a rare entity. The underlying pathogenetic mechanism of this association is unknown ¹. Here, we present a case who had JAK2 V617F mutation positive essential thrombocythemia (ET) and CLL simultaneously.

Case Report

A 75-year-old male patient was admitted to our haematology department with complaints of weakness and exercise intolerance lasting for two months. Physical examination findings were conjunctival pallor, 3/6 degrees aortic systolic ejection murmur, bilateral cervical and axillary lymphadenopathy and hepatosplenomegaly. Hemoglobin level was 4.9 gr/dL, hematocrit 18.2%, white blood cell count was 22.9x10⁹/L and platelet count was 1157x10⁹/L. The patient had absolute lymphocytosis with a number of 12.5x10⁹/L. The peripheral blood smear revealed hypochromia, 26% neutrophils, 70% lymphocytes, 2% monocytes, 2% eosinophils and smudge cells. Direct Coombs test was negative and no evidence of hemolysis was detected. Bone marrow aspiration and biopsy revealed erythroid hypoplasia, normal myeloid maturation, increased small mature lymphocytes with a percentage of 40% and also increased megakaryocytes with dysplastic changes. Flow cytometric analysis of bone marrow aspirate showed CD20 (60%), CD5 (80%), CD5-20 (59.7%), CD23 (54.1%) positivities supporting CLL. Thoracoabdominal computerized tomography scan showed no lymphadenopathy. 13q deletion and 17p deletion were negative by fluorescence in situ hybridization (FISH). BCR-ABL translocation was not detected by RT-PCR analysis and by FISH. JAK2 V617F mutation was detected heterozygous by PCR. ET and CLL were diagnosed simultaneously. We have separated the mononuclear cells from the heparinized venous blood of the patient by density gradient centrifugation method (Biocoll density 1.077 g/mL, isotone). JAK2 V617F mutation was negative in isolated lymphocytes by PCR. Hepatosplenomegaly was thought to be related with MPN. CLL stage was considered as Rai 1, Binet A. Hydroxyurea and acetylsalicylic acid treatment was started.

Discussion

MPNs are clonal haematopoietic stem cell disorders characterized by proliferation of one or more lineages of the myeloid, erythroid and megakaryocytic cell lines. The JAK2 V617F mutation is present in approximately 50-55% of the ET patients ^2,3. The risk of developing lymphoproliferative neoplasia is significantly increased in patients with MPN, especially harboring JAK2 V617F mutation ⁴. A retrospective multicenter study (Gruppo Italiano Malattie EMatologiche dell?Adulto - GIMEMA) reported 46 patients affected by CLL/ Monoclonal B-cell lymphocytosis (MBL) and concomitant MPN diagnosed between 1985-2010 ¹. Coexistence of CLL/MBL and ET was detected in 18 cases in this study. In review of the literature about coexistence of CLL and MPN (56 cases) in the same study, 12 cases had been reported as CLL/ET and ET occurred simultaneously or preceded the development of CLL ^4-10. However, GIMEMA series also demonstrated that ET could be subsequent to the diagnosis of CLL. The coexistence of these two distinct clonal haematological diseases raises the possibility of a common initiative pluripotent stem cell ^4,5. Henry et al. reported the absence of JAK2 V617F mutation in lymphoid cells of a case in whom CLL was diagnosed after ET and hydroxyurea treatment. The mutagenic role of hydroxyurea remains controversial and no increased frequency of lymphoproliferative neoplasia has been reported after hydroxyurea treatment ⁷. Kodali et al. reported the presence of JAK2 V617F mutation in B lymphocytes but not in T lymphocytes in a patient with CLL coexisting MPN simultaneously¹¹. Likewise, Eskazan et al. detected JAK2 V617F mutation in both lymphoid and myeloid lineages in a patient with CLL coexisting MPN simultaneously in 2011 ¹². Clonal involvement of lymphoid lineage is still controversial because of conflicting data.

In our patient, we did not detect JAK2 V617F mutation in lymphoid lineage cells. This situation reduces the possibility of a common initiative pluripotent stem cell theory for these two distinct clonal haematological diseases. It is likely that the association between CLL and ET is coincidental.

References

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