Consistent loss of heterozygosity at 14q32 in lymphoid blast crisis of chronic myeloid leukemia

Little is understood about the basic biological mechanisms that underlie th e reasons for acute transformation in chronic myeloid leukemia (CML). Progr ession of disease may include inactivation of one or more tumor suppressor genes (TSGs). A widely used methodology for indirectly detecting somatic in activation of TSGs is searching loss of heterozygosity (LOH) for polymorphi c loci located in or near the gene(s) of interest. We aimed to analyze DNA of chronic phase and blastic phase archive material of 15 CML patients for LOH using D1S-430, D2S123, D3S1611, D11S29, D14S65, D17S520, BAT 40 markers , the dinucleotide repeat located in the ABL gene and the trinucleotide rep eat located in the BCR gene (amplification of the trinucleotide in the BCR gene could not be succeeded). LOH was identified by a %50 lost of one of th e alleles intensity. LOH was detected with the ABL dinucletide repeat and D 2S123 marker in two patients and with the D14S65 marker in three patients. The three patients exhibiting LOH at the D14S65 locus, all proceeded throug h lymphoid blast crisis. The D14S65 marker is located at the 14q32 locus wh ich contains the immunglobulin heavy chain gene and the TCL1 oncogene. 14q3 2 abnormalities at the molecular level, may be predictive for lymphoid blas t crisis, whether or not they are detectable cytogenetically.