title: t(4;22)(q12;q11.2) involving presumptive platelet-derived growth factor receptor A and break cluster region in a patient with mixed phenotype acute leukemia.
abstract: The patient is a 45-year-old woman with a history of breast cancer who had been treated 1 year ago with radiation and chemotherapy. Flow cytometric analysis of bone marrow aspirate revealed 81% blasts positive for CD4, CD11c (partial), CD13, CD19 (partial), cytoplasmic CD22, CD34, CD36, CD45, cytoplasmic CD79a, CD117 (partial), HLA-DR, and terminal deoxynucleotide transferase, consistent with a mixed phenotype acute leukemia (B/myeloid lineage). Conventional karyotypic analysis revealed a t(4;22)(q12;q11.2) in 12 of 13 cells analyzed. Fluorescence in situ hybridization analysis using a dual-color, dual-fusion break cluster region/ABL probe set showed no break cluster region/ABL translocation but an extra break cluster region signal in 85% (170/200) of cells, consistent with a translocation involving the break cluster region gene at 22q11.2. A FIP1L1/CHIC2/platelet-derived growth factor receptor α deletion/fusion probe showed signal separation in 96.5% (193/200) of interphase nuclei. Reverse transcriptase-polymerase chain reaction using sense break cluster region primers and an antisense platelet-derived growth factor receptor α primer resulted in a product of approximately 590 base pairs, consistent with the presence of a break cluster region/platelet-derived growth factor receptor α fusion gene. Because of the presumptive platelet-derived growth factor receptor α translocation and its sensitivity to tyrosine-kinase inhibitor, the patient was treated with imatinib mesylate, cytarabine, and idarubicin as induction and maintenance therapy; and she has remained free of disease for 5 months since the initial diagnosis.
authors.affiliation: Department of Pathology, University of California San Diego Health Sciences, La Jolla, CA 92093-0987, USA. hywang2@ucsd.edu
authors.forename: Huan-You
authors.initials: HY
authors.lastname: Wang
authors.forename: John A
authors.initials: JA
authors.lastname: Thorson
authors.forename: H Elizabeth
authors.initials: HE
authors.lastname: Broome
authors.forename: Hooman H
authors.initials: HH
authors.lastname: Rashidi
authors.forename: Peter T
authors.initials: PT
authors.lastname: Curtin
authors.forename: Marie L
authors.initials: ML
authors.lastname: Dell'Aquila
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001549:Benzamides; D019457:Chromosome Breakage; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D000068877:Imatinib Mesylate; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D007621:Karyotyping; D015456:Leukemia, Biphenotypic, Acute / Q000188:drug therapy / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate; D020796:Receptor, Platelet-Derived Growth Factor alpha; D015255:Idarubicin