Oncology Probes

Chronic Myeloproliferative Disorders (CMPD)Chromosomal translocations in chronic myeloproliferativediseases (CMPD) almost invariably result inexpression of constitutively activated fusion tyrosinekinases. The hallmark of these diseases is CML, wherethe BCR/ABL activated tyrosine kinase results fromthe balanced reciprocal Philadelphia chromosometranslocation t(9;22).Chronic Myelogenous Leukemia (CML) - BCR/ABL t(9;22)CML is a malignant chronic myeloproliferative disorder (MPD)of the hematopoietic stem cell. All CML have a t(9;22) causingfusion of the 3’ ABL region at 9q34 with the 5’ BCR region at22q11. This chimeric BCR/ABL gene encodes a constitutivelyactivated protein tyrosine kinase with profound effects on cellcycle, adhesion, and apoptosis. Understanding this process hasled to the development of the drug imatinib mesylate (Gleevec),the first in a new class of genetically targeted agents, this is amajor advance in cancer treatment. Several different approachesare used to analyze the BCR/ABL t(9;22)(q34;q11) by FISH eachproviding different details about this translocation.BCR/ABL Product FamilyThe Philadelphia chromosome is an abnormally shortchromosome 22 that is one of the two chromosomes involvedin a translocation with chromosome 9. This translocation t(9;22)(q34;q11) takes place in a single bone marrow cell and, throughthe process of clonal expansion, gives rise to the leukemia.ABL and BCR are normal genes on chromosomes 9 and 22,respectively. The ABL gene encodes a tyrosine kinase enzymewhose activity is tightly controlled. In the formation of thePh translocation, two fusion genes are generated: BCR-ABLon the Ph chromosome and ABL-BCR on the chromosome 9participating in the translocation. The BCR-ABL gene encodesa protein with deregulated tyrosine kinase activity.The presence of this protein in the CML cells is strongevidence of its pathogenetic role. The efficacy in CMLof a drug that inhibits the BCRABL tyrosine kinase hasprovided the final proof that the BCR-ABL oncoprotein isthe unique cause of CML. The Poseidon portfolio containsnow 4 different probes for BCR/ABL to suit all needs forthe detection of t(9;22) by FISH:BCR/ABL t(9;22) Dual-color, Dual-Fusion ProbeD22S940SHGC-147754ASS340 KBIGLC1340 KBABLBCRInterpretationguidelines forPoseidonBCR/ABL ProbesNormal Cell t(9;22) positive Cryptic insertion 9q34 to 22q11BCR/ABL t(9;22) Triple-color, Dual-Fusion Probe99q34NUP214D9S19911000 KB2222q11IGLL1SHGC-1074501000 KBOncology Probes - Hematology ProbesNormal Cellt(9;22) positiveWith del(22q11)Normal Cellt(9;22) positivet(9;22) positiveWith del(9q34)BCR/ABL t(9;22) Dual-color, Single-Fusion Extra Signal Probet(9;22) positiveBCR/ABL t(9;22) Dual-color, Single-Fusion Probe99SHGC-147754ASSABLNUP2149q34 D9S1991SHGC-147754ASSABLNUP2149q34 D9S1991SHGC-147754ASSABLNUP2149q34 D9S1991340 KB1000 KB340 KB1000 KB340 KB1000 KB2222D22S940IGLC1BCRIGLL122q11SHGC-107450D22S940IGLC1BCRIGLL122q11SHGC-107450D22S940IGLC1BCRIGLL122q11340 KB1000 KB340 KB340 KB92212Normal Cellt(9;22) positive