Morphological, cytogenetic, and molecular features of a bone marrow sample from a 68‐year‐old Japanese woman with acute promyelocytic leukemia. (a) May–Giemsa staining. Promyelocytes with azurophilic granules and Auer rods are observed. (b) Interphase FISH using promyelocytic leukemia (PML) (15q22; green) and retinoic acid receptor α (RARA) (17q21; red) probes did not reveal a PML–RARA fusion signal (yellow). (c) Interphase FISH assay to detect RARA split signal (using 3′‐RARA [green] and 5′‐RARA [red] probes) showed no split signals but rather a small yellow signal (46/100; arrow). (d) mRNA expression of interferon regulatory factor 2 binding protein 2 (IRF2BP2) and IRF2BP2–RARA. Lane 1 shows the result of using two complementary oligonucleotide primers, FP1 and RP1. The upper detected band was predicted to be 206 bp and the lower band was predicted to be 158 bp; these bands were supposed to correspond to the expression of normal splice variants of IRF2BP2 in the patient's bone marrow. Lane 2 shows the result of FP1 and RP2. The upper detected band was predicted to be 398 bp and the lower band was predicted to be 350 bp; these bands were supposed to correspond to the expression of the fusion variants of IRF2BP2–RARA. (e) Direct sequencing of the PCR products. The sequences of each PCR product obtained in (d) were determined. The results confirmed that this patient expressed two variants of IRF2BP2 (data not shown), as well as the predicted fusion mRNAs of IRF2BP2–RARA; the upper and lower panels show the sequences of the fusion genes from IRF2BP2 variants 1 and 2, respectively. (f) Schematic illustrations of the transcripts. The blue and yellow solid bars represent the coding regions of the IRF2BP2 and RARA genes, respectively. IRF2BP2 generates the transcript variants through alternative splicing. Variant 1 uses an alternate in‐frame splice junction in the 3′‐ coding region of exon 1, resulting in an mRNA transcript 48 bp longer than variant 2. The inverted triangles represent each predicted fusion point on the transcript. The IRF2BP2–RARA fusion is expected to generate two types of fusion mRNA depending on the IRF2BP2 variants. In the longer type, base 1079 of the IRF2BP2
mRNA is likely to be fused to base 769 of the RARA
mRNA. In the shorter type, the base 1031 of the IRF2BP2
mRNA is likely to be fused to base 769 of the RARA
mRNA. (g) Overviews of genomic DNA of the IRF2BP2,RARA, and predicted IRF2BP2–RARA fusion genes.