A rare “common” acute lymphoblastic leukemia with t(17;19)(q22;p13) with extremely poor prognosis

Abstract

Hematologists should consider t(17;19)-positive ALL because patients with this rare type of common ALL have extremely poor prognosis when administered standard chemotherapy, even in combination with stem cell transplantation. TCF3::HLF (E2A-HLF) fusion transcription factor, produced by 17;19 translocation, protects leukemic cells from apoptosis, causing the extremely refractory nature of ALL harboring this translocation despite a relatively low WBC count at diagnosis. Clinicians must pay attention to the chromosomal analysis report because patients with 17;19 translocation are frequently misdiagnosed as having a normal karyotype. TCF3::HLF aberrantly induces the expression of many genes, including those encoding apoptosis regulators, LMO2, CD33, and ANNEXIN II. Consequently, more than half the patients with t(17;19)-ALL express CD33 on the surface of leukemic cells and have hypercalcemia or coagulopathy, all of which are relatively rare in common ALL. Thus, RT-PCR to detect TCF3::HLF chimeric transcript should be performed for patients with common ALL with normal karyotype, particularly for those who have the above-mentioned clinical features. Patients positive for TCF3::HLF chimeric fusion transcript should undergo powerful cutting-edge treatments, including CAR-T cell therapy and blinatumomab.