title: Novel variant Ph translocation t(9;22;11)(q34;q11.2;p15)inv(9)(p13q34) in chronic myeloid leukemia involving a one-step mechanism.
abstract: Chronic myeloid leukemia (CML) is a clonal malignant disorder of a pluripotent hematopoietic stem cell characterized by the presence of a Philadelphia (Ph) chromosome. Less than 10% of patients present variant Ph chromosomes involving 1 or more additional chromosomes, other than chromosomes 9 and 22, with uncertain prognosis. There are mainly 1- or 2-step mechanisms proposed to explain the genesis of variant Ph chromosomes depending on whether the involved chromosomes are simultaneously broken and rejoined or if a standard t(9;22) occurs first. By combined standard cytogenetic and FISH analysis we detected a novel variant Ph translocation among chromosomes 9, 11 and 22 in a patient with CML without progression to an accelerated phase of the disease after 7 years, with the derivative chromosome 9 also having an acquired pericentric inversion. This novel case illustrates the use of FISH in metaphase to confirm a new rearrangement not previously described in variant Ph formation and that the present karyotype could have originated by a 1-step mechanism with 4 simultaneous breakages without deletion of ABL1.
authors.affiliation: Departamento de Genética, Instituto de Investigaciones Hematológicas 'Mariano R. Castex', Academia Nacional de Medicina, Buenos Aires, Argentina. cbelli@hematologia.anm.edu.ar
authors.forename: C
authors.initials: C
authors.lastname: Belli
authors.forename: M F
authors.initials: MF
authors.lastname: Alú
authors.forename: G
authors.initials: G
authors.lastname: Alfonso
authors.forename: M
authors.initials: M
authors.lastname: Bianchini
authors.forename: I
authors.initials: I
authors.lastname: Larripa
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D002871:Chromosome Banding; D007446:Chromosome Inversion / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D000069439:Dasatinib; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D007371:Interferon-gamma / Q000627:therapeutic use; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D008677:Metaphase; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D007371:Interferon-gamma; D000068877:Imatinib Mesylate; D000069439:Dasatinib; D006918:Hydroxyurea