Characterization of a 14q +marker chromosome in Philadelphia chromosome positive acute lymphoblastic leukemia by DNA analysis and fluorescence in situ hybridization

We report a case of precursor-B acute lymphoblastic leukemia (ALL) with the Philadelphia chromosome (Ph) and a 14q+ chromosome whose additional material was a part of the long arm of der(9)t(9;22). A minor population carrying the standard Ph translocation without the 14q+ was also observed at the first presentation. The translocation of the BCR gene from chromosome 22 to the subtelomeric region of the 14q+ was confirmed by fluorescence in situ hybridization (FISH) using a yeast artificial chromosome (YAC) clone containing the BCR gene. The breakpoint of chromosome 14 could not be determined exactly but probably was at 14824 or 14832 by conventional chromosome analysis. Nevertheless, FISH using a YAC clone containing the human immunoglobulin heavy chain (IgH) gene locus, Southern blot, and pulsed field gel electrophoresis (PFGE) analyses with IgJH probe, and loss of heterozygosity analysis at the α1-antitrypsin (AT) gene locus showed lack of involvement of the IgH gene in the 14q+ and more centromeric breakage than the a1-AT locus at 14832.1. Thus, the formation of the 14q+ seemed to be a secondary genetic event after the Ph translocation and presumably played a minor role in the pathogenesis of B-cell malignancy in this case.