Cytogenetic, spectral karyotyping, fluorescence in situ hybridization, and comparative genomic hybridization characterization of two new secondary leukemia cell lines with 5q deletions, and MYC and MLL amplification.
Cytogenetic studies of patients with therapy-induced acute myeloid leukemia (t-AML) have demonstrated whole chromosome loss or q-arm deletion of chromosomes 5 and/or 7 in a majority of cases. We have established two cell lines, SAML-1 and SAML-2, from two patients who developed t-AML after radiation and chemotherapy for Hodgkin disease. In both cases, the leukemia cells contained 5q deletions. SAML-1 has 58 chromosomes and numerous abnormalities, including der(1)(1qter-->1p22::5q31-->5qter), der(5)(5pter-->5q22::1p22-->1pter), +8, der(13)i(13)(q10)del(13)(q11q14.1), and t(10;11). Fluorescence in situ hybridization (FISH) with unique sequence probes for the 5q31 region showed loss of IL4, IL5, IRF1, and IL3, and translocation of IL9, DS5S89, EGR1, and CSFIR to 1p. SAML-2 has 45 chromosomes, del(5)(q11.2q31) with a t(12;13)ins(12;5), leading to the proximity of IRF1 and RB1, and complex translocations of chromosomes 8 and 11, resulting in amplification of MYC and MLL. Comparative genomic hybridization and spectral karyotyping were consistent with the G-banding karyotype and FISH analyses. Because a potential tumor suppressor(s) in the 5q31 region has yet to be identified, these cell lines should prove useful in the study of the mechanisms leading to the development of t-AML.
Knutsen
Turid
T
Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. knutsent@mail.nih.gov
Pack
Svetlana
S
Petropavlovskaja
Maria
M
Padilla-Nash
Hesed
H
Knight
Clement
C
Mickley
Lyn A
LA
Ried
Thomas
T
Elwood
Patrick C
PC
Roberts
Susan J
SJ
D000208:Acute Disease; D000328:Adult; D002871:Chromosome Banding; D020223:Chromosome Painting; D020732:Cytogenetic Analysis; D006689:Hodgkin Disease / Q000150:complications* / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping / Q000379:methods; D007951:Leukemia, Myeloid / Q000150:complications / Q000235:genetics*; D007953:Leukemia, Radiation-Induced / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods; D010641:Phenotype; D014407:Tumor Cells, Cultured