title: The prognostic significance of an inv(3)(q21q26.2) in addition to a t(9;22)(q34;q11.2) in patients treated with tyrosine kinase inhibitors.
abstract: In chronic myelogenous leukemia, BCR-ABL1 positive detection of cytogenetic abnormalities in addition to the t(9;22) is thought to portend a poor prognosis; however, not all abnormalities associated with the t(9;22) have the same impact. Inv(3) defines a group of aggressive neoplasms with poor response to conventional treatment options. In this study, four cases with the t(9;22) and inv(3) treated with tyrosine kinase inhibitors (TKI) were investigated. In three cases, the inv(3) was not detected at the initial diagnosis and the patients initially responded to TKI therapy; the inv(3) was detected at blast crisis in all three cases, and one case had both abnormalities at the initial presentation, but this case presented as acute myeloid leukemia. In all cases, detection of an inv(3) was associated with a high blast count and a lack of response to treatment regimens including TKI. All patients died within months from the detection of inv(3). This indicates that cases with the t(9;22) and inv(3) have a clinical course similar to that of cases with an inv(3) and no other therapeutically targetable abnormality.
authors.affiliation: R.J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH.
authors.forename: Karl S
authors.initials: KS
authors.lastname: Theil
authors.affiliation: R.J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH. Electronic address: cottac@ccf.org.
authors.forename: Claudiu V
authors.initials: CV
authors.lastname: Cotta
mesh_terms: D000368:Aged; D001752:Blast Crisis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D007446:Chromosome Inversion / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D010677:Philadelphia Chromosome; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D014178:Translocation, Genetic
chemical_list: D047428:Protein Kinase Inhibitors
keywords: Philadelphia chromosome; blast crisis; clonal evolution; inv(3); t(9;22)