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Identification of PML/RAR�± fusion gene transcripts that showed no t(15;17) with conventional karyotyping and fluorescent in situ hybridization

Author(s): A. Choughule S. Polampalli P. Amre S. Shinde S. Banavali K. Prabhash R. Nair P.G. Subramanian S. Gujral P.M. Parikh

Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation, t(15;17)(q22;q11-21), resulting in the fusion of the promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARα) genes. Using conventional cytogenetic methods, these translocations are normally detected in about 70-90% of patients; most negative results are due to technical problems or cryptic variants. These masked PML/RARα fusions can be identified by molecular analyses, such as reverse transcriptase-polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH). Approximately 5 to 10% of all APL cases reported do not show PML/RARα fusion transcripts, even with dual-colored FISH. We report three of 40 diagnosed APL cases that showed morphological, cytochemical, and immunophenotypic features of hypergranular APL, but did not show a PML/RARα fusion signal or any of its variants, on FISH. All cases were identified by RT-PCR, which was further confirmed by cDNA sequencing. Conventional karyotyping showed other clonal aberrations in these cases, but failed to show t(15;17) or any other variants or complex translocations. Acute promyelocytic leukemia (APL) is characterized by a reciprocal translocation, t(15;17)(q22;q11-21), resulting in the fusion of the promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARα) genes. Using conventional cytogenetic methods, these translocations are normally detected in about 70-90% of patients; most negative results are due to technical problems or cryptic variants. These masked PML/RARα fusions can be identified by molecular analyses, such as reverse transcriptase-polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH). Approximately 5 to 10% of all APL cases reported do not show PML/RARα fusion transcripts, even with dual-colored FISH. We report three of 40 diagnosed APL cases that showed morphological, cytochemical, and immunophenotypic features of hypergranular APL, but did not show a PML/RARα fusion signal or any of its variants, on FISH. All cases were identified by RT-PCR, which was further confirmed by cDNA sequencing. Conventional karyotyping showed other clonal aberrations in these cases, but failed to show t(15;17) or any other variants or complex translocations.