MEF2D-rearranged acute lymphoblastic leukemia resembles Burkitt lymphoma/leukemia

Abstract

Dear Editor, Burkitt lymphoma/leukemia (BL) is one clinically aggressive hematological malignancy, and it is characterized by the morphology of monotonous medium-sized cells containing abundant basophilic cytoplasm and lipid vacuoles, as well as round nuclei with multiple nucleoli and clumped chromatin, the immunophenotype of mature B cell, and MYC rearrangement leading to its overexpression [1]. Interestingly, some acute lymphoblastic leukemia (ALL) could resemble BL in clinic, but the mechanism remained unknown. MEF2D rearrangement is frequent in B-cell ALL, and its targets mainly involved BCL9, CSF1R, DAZAP1, HNRNPUL1, SS18, STAT6, FOXJ2, and HNRNPUH1 [2–6]. It has been demonstrated that MEF2D rearrangement conferred an inferior prognosis for ALL [7], but the clinical and genetic features of MEF2D-rearranged B-cell ALL still remained not well-defined. Herein, we reported two MEF2Drearranged B-cell ALL patients presenting as the BLlike disease. One 35-year-old female patient presented fatigue and eyelid as well as lower extremity edema. Peripheral blood (PB) exhibited WBC, 6.9 × 10/L; HB, 97 g/L; PLT, 211 × 10/L; and circulated blast, 20%. Morphologic examination found 80% lymphoblast, belonging to ALL-L3 subtype, in bone marrow (BM) (Fig. 1A). We defined the immunophenotype of lymphoblast as CD5-CD7CD10+CD19+CD20+CD22+CD24+CD25CD34-CD38+CD103-CD117-CD200+HLA-DR+ (Fig. 1B). Besides, its karyotype was normal, and t(8;14) was negative (Fig. 1C). To understand its pathogenesis and to found its driver genetic event, we displayed RNAsequencing and identified MEF2D-BCL9 (Fig. 1D). Therefore, BL-like ALL with MEF2D rearrangement but not BL was diagnosed. Immediately, she was treated with the VICP regimen (doxorubicin in VDCP regimen was replaced by idarubicin) [8], and a complete remission (CR) was obtained. Then, she received three additional VICP regimens and one VP-E-medium-dose cytarabine regimen. CR was still maintained at 8-month later. A 44-year-old male patient presented with fatigue, poor appetite, gingival bleeding, and purpura all lasting for over 1 week. PB examination found WBC, 37.6 × 10/ L; HB, 115 g/L; PLT, 26 × 10/L; circulated blast, 83%; and LDH, 5407 U/L. BM aspiration identified 82% primitive and immature lymphocytes, belonging to ALL-L3 subtype (Fig. 1E). Subsequently, immunophenotypic analysis showed CD7-CD10+CD19+CD20+CD22+ CD24+CD25-CD34-CD58+cytoCD79a+CD117CD200+nTdT-cytoIgM(Fig. 1F). Cytogenetic analysis exhibited 48,XY,– 3,+ 3mar[1]/50,idem,+ 2mar[1], but t(8;14) was negative (Fig. 1G). Though its morphologic feature was the same as BL, the immunophenotype and genetic feature did not support this diagnosis. Therefore, we displayed RNA-sequencing, and MEF2DHNRNPUL1 was identified (Fig. 1H). So, this patient was Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00277-019-03857-x) contains supplementary material, which is available to authorized users.