The genetic hallmark of acute promyelocytic leukemia (APL) is the balanced reciprocal chromosomal translocation of (15;17) leading to a fusion of the promyelocytic leukemia (PML) gene on chromosome 15 and the retinoic acid receptor-á (RARá) gene on chromosome 17 [1]. Identification of PML/RARá fusion gene by reverse transcriptase-polymerase chain reaction (RT-PCR) without evidence of t(15;17) both on conventional karyotype and fluorescence in situ hybridization (FISH) is rare [2,3].

Cytochemical staining with myeloperoxidase was strongly positive. Child was diagnosed morphologically as AML-M3 (hypergranular variant). Immunophenotyping analysis of the bone marrow cells was consistent with APL. Conventional cytogenetic analysis showed 46, XY, isochromosome (17q). FISH analysis was negative for t(15;17). RT-PCR was positive for PML–RARá fusion transcripts. She had completed both induction and consolidation phase of all-trans retinoic acid (ATRA) based chemotherapy regimen. Child responded dramatically and went into molecular remission.

Conventional cytogenetic analysis can identify reciprocal chromosomal translocation t(15;17) in upto 90% of cases with APL. The remaining 10% cases lacking t(15;17) stay associated with the cryptic insertion of the PML/RARá fusion gene [4,5]. FISH analysis and RT- PCR are the valuable tools to identify the PML/RARá hybrid transcript in a cytogenetically negative APL patient. The routinely used dual-colored break apart probes that are used in FISH are not sensitive enough to hybridize with such small cryptic insertions and therefore do not produce a signal as in our case. However, these small cryptic insertions can be amplified and detected by RT-PCR. These RT-PCR positive cases for hybrid PML/RARá transcript classify a new cytogenetic subgroup of APL.

We suggest that RT-PCR should be performed at baseline to detect this small subset of t(15;17) negative APL cases, with cryptic or masked insertions.

1. Duan Y, Nie J, Zhang Z, Zhou L, Zhu F, Zhang H, et al. A rare case with typical acute promyelocytic leukemia morphology associated with isolated isochromosome 17q without RARá rearrangement. Hematol Oncol Stem Cell Ther. 2013;6:42-5.

2. Huh J, Moon H, Chi H, Chung W. Acute promyelocytic leukemia with i(17)(q10) on G-banding and PML/RARA rearrangement by RT-PCR without evidence of PML/RARA rearrangement on FISH. Int J Lab Hematol. 2009;31:372-4.

3. Choughule A, Polampalli S, Amre P, Shinde S, Banavali S, Prabhash K, et al. Identification of PML/RARalpha fusion gene transcripts that showed no t(15;17) with conventional karyotyping and fluorescent in situ hybridization. Genet Mol Res. 2009;8:1-7.

4. Zaccaria A, Valenti A, Toschi M, Salvucci M, Cipriani R, Ottaviani E, et al. Cryptic translocation of PML/RARA on 17q. A rare event in acute promyelocytic leukemia. Cancer Genet Cytogenet. 2002;138:169-73.