A 15-year-old boy complained of abdominal pain, weakness and intermittent fever. Laboratory investigation values are depicted in Table 1. Bone marrow examination revealed abnormal promyelocytes with regular, round to oval nuclei, (lacking the classical bilobed appearance) dense cytoplasmic granularity, the absence of Auer rods but strong cytochemical myeloperoxidase (MPO) positivity (Figure 2, A & B). Few Pelger-like neutrophils were also observed along with maturing myeloid cells. The patient did not develop any bleeding manifestations. FCI revealed cells having high side scatter and dim CD45 expression, heterogeneous CD13, and homogeneous bright CD33, along with lack of CD34, HLA-DR, and CD56 expression. FISH was negative for t(15;17). The RARA break-apart probe detected a variant RARA translocation. PCR for PML-RARA fusion transcripts was negative as well. ZBTB16 as the partner gene for variant RARA was confirmed with PCR. The patient received induction with Idarubicin and arsenic trioxide (ATO). Forty-five days post induction remission was not achieved.
FISH showed variant RARA positivity in 52% cells. RT-qPCR showed mean threshold cycle (Ct) value of 26.78 against a baseline Ct value of 21.42 for ZBTB16-RARA and 21.03 for ABL1. The patient further received three cycles of high dose cytarabine (HiDAC) following which complete remission was achieved with no detectable ZBTB16-RARA fusion transcripts.