Ph1-positive acute leukemia with a 17q;21q translocation

104

A human c-erbA oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia (somatic cell Contributed by Peter C. Nowell, April 5, 1984 ABSTRACT A human cDNA library was screened for sequences homologous to the erbA gene of avian erythroblastosis virus (AEV). One such clone, cHerbA-1, was used to map the chromosomal location of highly homologous human sequences that were found to be present on chromosome 17 as judged by Southern blot screening of a panel of mouse-human hybrid cell lines segregating human chromosomes. cHerbA-1 was hybridized in situ to metaphase chromosomes from a normal male subject and from a female patient with an acute promyelocytic leukemia (APL) having the typical t(15;17) translocation. The results localized the cellular c-erbA sequences on chromosome 17 to the q21-q24 region of normal chromosomes and indicated that the c-erbA sequences remained on the 17q-chromosome in the APL cells, suggesting that they could be assigned to the 17(q21-q22) region. For additional data, we hybridized human neoplastic cells derived from a poorly differentiated acute leukemia carrying a t(17;21) translocation with thymidine kinase (TK)-deficient LMTK-mouse cells. A resulting hybrid, containing only the 21q+ chromosome, did not have human c-erbA sequences. Since the breakpoint on 17q in this translocation was similar to that in the APL t(15;17) translocation, this supported the assignment of c-erbA to the q21-q22 region of chromosome 17. The apparent close proximity of the c-erbA sequences to the chromosomal breakpoints in these two leukemias suggests a possible role for this oncogene homologue in the development of these neoplasms.

Section: Methodsmentioning

confidence: 99%

A human c-erbA oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia.

Dayton¹,

Selden²,

Laws³

et al. 1984

104

“…A similar chromosome 17 breakpoint was described in a human leukemia with both 17;21 and 9;22 reciprocal translocations (40). It is interesting that a fragile site on chromosome 17 (p12) is situated near the p53 locus, but we are unaware of any reported tumor-specific chromosome aberrations involving the short arm of chromosome 17.…”

Section: Resultsmentioning

confidence: 92%

The gene for human p53 cellular tumor antigen is located on chromosome 17 short arm (17p13).

McBride¹,

Merry²

1986

277

108

A clone that cross-hybridizes with a mouse p53 probe has been isolated from a cDNA library of simian virus 40-transformed human fibroblasts. This cloned human p53 cDNA was used as a probe to examine DNAs obtained from human-rodent somatic cell hybrids that have segregated human chromosomes. The results show that the human p53 gene is located on chromosome 17. In addition, Southern analysis of hybrids prepared from human cells containing a chromosome 17 translocation allowed regional localization of the human p53 gene to the most distal band on the short arm of this chromosome (17p13). Localization of the p53 gene to 17pl3 was confirmed by in situ hybridization of metaphase spreads with the human p53 probe.

“…Tumor cells from'two patients with APL (designated C and S) with the characteristic t(15;17)(q22;q21) marker chromosomes (15,16) and one patient with undifferentiated acute leukemia, designated L, with a t(17;21)(q21;q22) chromosome (18,28) were also studied. The 275S hybrid cell line has been described and was isolated after fusion of the human leukemia L tumor cells with mouse L-M(TK-) cells.…”

mentioning

confidence: 99%

“…4) derived from a patient with undifferentiated acute leukemia (28) in a mouse L-M(TK-) background (18). The breakpoint in chromosome 17 in this tumor was considered identical with that of the characteristic t(15;17) chromosome translocation breakpoint of APL (28). The leukemia-derived and hybrid DNA containing filters were hybridized with an NGFR cDNA clone (Fig.…”

mentioning

confidence: 99%

“…We have carried out Southern analysis of HindIII and EcoRI cleaved DNAs derived from leukemia patients and from a mouse-human hybrid (275S) retaining only a 21q+ (21pter-21q22::17q21-qter) chromosome (see Fig. 4) derived from a patient with undifferentiated acute leukemia (28) in a mouse L-M(TK-) background (18). The breakpoint in chromosome 17 in this tumor was considered identical with that of the characteristic t(15;17) chromosome translocation breakpoint of APL (28).…”

mentioning

confidence: 99%

See 1 more Smart Citation

The nerve growth factor receptor gene is at human chromosome region 17q12-17q22, distal to the chromosome 17 breakpoint in acute leukemias.

Huebner

Isobe

Chao

et al. 1986

Genomic and cDNA clones for the human nerve growth factor receptor have been used in conjunction with somatic cell hybrid analysis and in situ hybridization to localize the nerve growth factor receptor locus to human chromosome region 17ql2-q22. Additionally, part, if not all, of the nerve growth factor receptor locus is present on the translocated portion of 17q (17q21-qter) from a poorly differentiated acute leukemia in which the chromosome 17 breakpoint was indistinguishable cytogenetically from the 17 breakpoint observed in the t(15;17)(q22;q21) translocation associated with acute promyelocytic leukemia. Thus the nerve growth factor receptor locus may be closely distal to the acute promyelocytic leukemia-associated chromosome 17 breakpoint at 17q21.