A variant acute promyelocytic leukemia with t(11;17) (q23;q12);ZBTB16-RARAshowing typical morphology of classical acute promyelocytic leukemia

Abstract

A subgroup of acute leukemia with morphology resembling acute promyelocytic leukemia (APL) shows variant translocations involving RARA and has a different morphology from that of classical APL. The variant APL with t(11;17)(q23;q12); ZBTB16-RARA subgroup has been reported to have leukemic cells with regular nuclei, many granules, absence of Auer rods, an increased number of Pelgeroid neutrophils, strong myeloperoxidase (MPO) activity, and all-trans-retinoic-acid (ATRA) resistance. Here, we report a case of variant APL with t(11;17)(q23;q12); ZBTB16-RARA showing typical morphological features of classical APL, including numerous Auer rods and faggot cells. The leukemic cells expressed CD13, CD33, CD117, human leukocyte antigen (HLA)-DR, and cytoplasmic-MPO on the immunophenotyping study. The diagnosis was confirmed by cytogenetic and molecular studies. To distinguish variant APL cases from classical APL cases, regardless of whether morphologically the findings are consistent with those of classical APL, combining morphologic, immunophenotypic, cytogenetic, and molecular studies before chemotherapy is very important.

Current views on the genetic landscape and management of variant acute promyelocytic leukemia

“…PLZF locates at chromosome 11q23, and t(11;17)(q23;q21) generated PLZF-RARA and RARA-PLZF . Notably, PLZF-RARA was the most common variant RARA rearrangement accounting 1% of APL, and various cases have been reported up to now, while its breakpoint was relatively conserved and only two isoforms were identified [ 23 – 28 ]. PLZF-RARA could block the myeloid differentiation and lead to leukemic transformation [ 29 ].…”

Molecular Profiling: A Case ofZBTB16-RARAAcute Promyelocytic Leukemia

“…Identification of the t(11;17) at the cytogenetic and/or the ZBTB16-RARA fusion at the cytogenetic and molecular levels, respectively, is paramount as, in the case described herein, ZBTB16-RARA APL is generally unresponsive to ATRA therapy, although it must be noted that some response to initial ATRA therapy has been documented in very rare cases and always in combination with other agents [ 17 – 19 ]. Although distinctive morphological features have been ascribed to ZBTB16-RARA APL [ 6 ], the peripheral blood and bone marrow morphology in this case more closely resembled that of typical APL, an aspect infrequently reported [ 20 ].…”

MLL‐ELL fusion gene in an acute myelomonocytic leukemia patient transformed from acute promyelocytic leukemia

“…Although t(15;17) is almost always associated with APL, a small proportion of patients with APL have simple or complex variants of this translocation. These variant chromosomal translocations include t(11;17)(q23;q21) and t(5;17)(q35;q21), leading to PLZF‐RAR α and NPM1‐RAR α fusions , respectively. In the M4 case, early experiments did not detect any signs of PML‐RAR α (including bcr1, 2, 3) fusion or PLZF‐RAR α and NPM1‐RAR α fusions (Table ).…”