Consistent loss of heterozygosity at 14Q32 in lymphoid blast crisis of chronic myeloid leukemia.
Little is understood about the basic biological mechanisms that underlie the reasons for acute transformation in chronic myeloid leukemia (CML). Progression of disease may include inactivation of one or more tumor suppressor genes (TSGs). A widely used methodology for indirectly detecting somatic inactivation of TSGs is searching loss of heterozygosity (LOH) for polymorphic 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 D1S430, D2S123, D3S1611, D11S29, D14S65, D17S520, BAT 40 markers, the dinucleotide repeat located in the ABL gene and the trinucleotide repeat 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 the alleles intensity. LOH was detected with the ABL dinucleotide repeat and D2S123 marker in two patients and with the D14S65 marker in three patients. The three patients exhibiting LOH at the D14S65 locus, all proceeded through lymphoid blast crisis. The D14S65 marker is located at the 14q32 locus which contains the immunoglobulin heavy chain gene and the TCL1 oncogene. 14q32 abnormalities at the molecular level, may be predictive for lymphoid blast crisis, whether or not they are detectable cytogenetically.
Sercan
H O
HO
Department of Medical Biology, Dokuz Eylül University Faculty of Medicine Izmir, Turkey. ogun.sercan@deu.edu.tr
Sercan
Z Y
ZY
Kizildag
S
S
Undar
B
B
Soydan
S
S
Sakizli
M
M
D000328:Adult; D000368:Aged; D001752:Blast Crisis / Q000209:etiology / Q000235:genetics*; D001853:Bone Marrow; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D015342:DNA Probes; D018450:Disease Progression; D005260:Female; D005803:Genes, Immunoglobulin / Q000235:genetics; D016313:Genes, abl; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics
D015342:DNA Probes; D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human