BCR/ABL1 fluorescence in situ hybridization fusion signals on both copies of chromosome 22 in a Philadelphia-masked chronic myeloid leukemia case: implication for the therapy

Abstract

The cytogenetic hallmark of Chronic Myeloid Leukemia (CML) is the presence of Philadelphia (Ph) chromosome, which results from a reciprocal translocation t(9;22)(q34;q11). In this report, we describe a CML patient with no evidence of Ph chromosome but trisomy of chromosome 8 as single cytogenetic abnormality and a typical e14a2 (b3a2) BCR-ABL1 fusion transcript. Fluorescence In Situ Hybridization (FISH) analysis revealed an uncommon signal pattern: the fusion signals were located on both copies of chromosome 22. During the course of the disease the appearance of the p.(Tyr315Ile) mutation was recorded. To the best of our knowledge this is the first Ph chromosome-negative CML case with e14a2 (b3a2) BCR-ABL1 transcript and p.(Tyr315Ile) mutation.

Keywords: CML; Chronic Myeloid Leukemia; Philadelphia chromosome-negative; masked Philadelphia; p.(Tyr315Ile) mutation.

Figure 1.

Quinacrine-banded metaphase cell from peripheral blood showing a 47 chromosomes male karyotype with trisomy of chromosome 8. Chromosomes 9 and 22 look normal.

Figure 2.

A) FISH on interphase cells from peripheral blood hybridized with locus specific probe LSI BCR/ABL1 Dual Color/Dual Fusion (Vysis/Abbott, Illinois, USA), showing one normal nucleus with 2 red signals (ABL1 gene, 9q34.12) and two green signals (BCR gene, 22q11.23) and one abnormal nucleus with two red signals, and two fusion signals (red/green or yellow). B) FISH on metaphase cell, hybridized with locus specific probe XL BCR/ABL1 plus Translocation/Dual Fusion Probe (MetaSystems, Althlussheim, Germany) showing two red signals on chromosomes 9, two fusion signals on both chromosomes 22. C) Image B with spectrum orange filter. D) Image B with spectrum green filter.