Cryptic to conventional cytogenetics: Philadelphia-like ALL presenting with hypereosinophilia

Abstract

BCR::ABL1-like B-lymphoblastic leukaemia (B-ALL) neoplasms lack the BCR::ABL1 translocation but have a gene expression profile like BCR::ABL1 positive B-ALL. This includes alterations in cytokine receptors and signalling genes, such as CRLF2, ABL1, ABL2, JAK2, PDGFRB and EPOR Cases with CRLF2 rearrangements account for approximately 50% of cases of Philadelphia-like acute lymphoblastic leukaemia (Ph-like ALL), and the frequency of specific genomic lesions varies with ethnicity such that IGH::CRLF2 translocations are more common in Hispanics and Native Americans.We report two cases of BCR::ABL1-like ALL, with significant eosinophilia. A Hispanic man in his early 20s and a Hispanic woman in her 50s presented with leukocytosis and eosinophilia. Bone marrow flow cytometry revealed lymphoblasts expressing CD19, CD10, partial CD20, CD22, CD79a, CD38, CD34, TdT and HLA-DR. Examination of the bone marrow biopsy and aspirate exhibited a hypercellular bone marrow with increased blasts and elevated eosinophils. Fluorescence in situ hybridisation (FISH) demonstrated a cryptic chromosomal rearrangement between the X chromosome and chromosome 14 at breakpoints involving IGH at 14q32 and CRLF2 at Xp22.33, t(X;14)(p22.33; q32).These findings confirmed the diagnosis of BCR::ABL1-like B-ALL with IGH::CRLF2 rearrangement. One patient (man) attained complete remission with induction therapy using the paediatric CALGB 10403 protocol, while the other patient (woman) had a poor outcome after receiving a hyper-fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone regimen. These two cases demonstrate an unusual presentation of BCR::ABL1-like B-ALL and emphasise the importance of appropriate cytogenetic studies for correct diagnosis. When treated with conventional chemotherapy, these cases carry a poor prognosis and might require allogeneic transplantation.

Keywords: Cancer - see Oncology; Haematology (incl blood transfusion); Malignant and Benign haematology; Pathology.

Figure 1. Rearrangement of CRLF2 gene at Xp22.33 on metaphase FISH study (A) and interphase FISH study (B) using CRLF2 breakapart probe.Rearrangement of IGH gene at 14q32.3 on metaphase FISH study (C) and interphase FISH study (D) using IGH breakapart probe.