Molecular methods for genomic analyses of variant PML-RARA or other RARA-related chromosomal translocations in acute promyelocytic leukemia

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Molecular methods for genomic analyses of variant PML-RARA or other RARA-related chromo-somal translocations in acute promyelocytic leukemia TO THE EDITOR: We read an interesting paper by Palta et al. in a recent issue of the Korean Journal of Hematology titled, " ZBTB16-RARA variant of acute promyelocytic leuke-mia with tuberculosis: a case report and review of literature " [1]. We would like to add some comments to their article and suggest additional molecular methods to confirm variant translocations in acute promyelocytic leukemia (APL). Apart from its characteristic morphology, APL is strongly correlated with presence of the PML-RARA fusion gene due to a t(15;17) translocation. Patients displaying cryptic PML-RARA gene rearrangements or other translocations involving RARA are very rare. Since RARA generates chi-meric fusion genes with various partners such as ZBTB16 at 11q23, NUMA1 at 11q13, NPM1 at 5q35, FIP1L1 at 4q12, and STAT5b at 17q11.2 (Fig. 1), confirmatory molecular methods to detect gene rearrangements are necessary when unique or unusual chromosomal translocations are found in APL cases. Palta et al. reported a case of APL accompanied by tuberculosis where cytogenetic study showed a variant chromosomal translocation, t(11;17)(q23;q21). First, although they describe this case as APL with t(11;17)(q23;q21) through bone marrow (BM), immunophenotyping, and cy-togenetic studies, we noted an absence of results based on molecular methods. To demonstrate the existence of the ZBTB16-RARA fusion gene, a single specific reverse tran-scriptase-polymerase chain reaction (RT-PCR) with a specific primer to detect the gene rearrangement or multiplex RT-PCR (e.g. HemaVision) to detect ZBTB16-RARA could have provided an accurate molecular diagnostic result. Second, the authors' reference to a paper by Kang et al. was puzzling despite the fact that it was cited as a similar case with chromosomal translocations at a similar location, in cases of AML with chromosomal translocation t(11;17) [2]. In the first case, cytogenetic analysis from BM aspirate showed t(11;17)(q23;q21) in 18 out of 20 cells while the MLL probe in fluorescence in situ hybridization (FISH) showed split-out signals in 98.5% of interphase cells. The second case also showed t(11;17)(q23;q25) in the chromosome study while the FISH assay showed split-out signals in 79% of interphase cells. However, normal fluorescence patterns were found in 200 cells in additional FISH assays when a dual-color single-fusion PML-RARA probe was used for both cases, which led to the conclusion …