This is a thirty-five year old man with pancytopenia and DIC currently being treated for presumed acute promyelocytic leukemia but FISH analysis and karyotype did not show any evidence of underlying t(15;17) translocation. The patient is on ATRA since this marrow and at the time of this review with good response so far.

CBC corresponding to this marrow indicates Hb=10.5 g/dL; WBC=1.4 k/uL and Platelet=21 k/uL.

Karyotype studies showed 46,XY,t(1;11)(p32;q23),del(13)(q12q22)[6]/46,XY[14] while there was no evidence of PML-RARA fusion using a dual fusion probe but RT-PCR demonstrated evidence of a PML-RARA fusion confirming that this is indeed the classic variant albeit cytogenetically negative with underlying cryptic translocation likely related to submicroscopic insertion/fusions below the threshold of detection of the FISH fusion probes used. Such cases while exceedingly rare, have been described in the context of APL and usage of smaller RARA break-apart probes and/or RT-PCR are both useful in identifying most if not all cases cytogenetically negative via dual fusion probes.[1]

REF:

1: Rashidi A, Fisher SI. FISH-negative, cytogenetically cryptic acute promyelocytic leukemia. Blood Cancer J. 2015 Jun 19;5:e320.

Learning points:

1. Acute promyelocytic leuekemia often presents with pancytopenia and DIC and harbors underlying t(15;17) translocation involving PML and RARA genes. Rare cases with classica translocation may be cytogenetically negative but detectable by RT-PCR.
2. They respond exquisitely to ATRA and arsenic combination therapy. Cases with variant translocation (involving PLZF/ZBTB15, or STAT5B may have suboptimal response to this therapy.
3. By flow cytometry, leukemic promyelocytes often lack CD34 and HLA-DR. When both are positive, microgranular variant must be considered.