scispace - formally typeset
Search or ask a question

Showing papers by "Todd R. Golub published in 1998"


Journal ArticleDOI
TL;DR: Mouse chimeras generated with TEL-/- ES cells establish TEL as the first transcription factor required specifically for hematopoiesis within the bone marrow, as opposed to other sites of hematoietic activity during development.
Abstract: The TEL (translocation-Ets-leukemia or ETV6) locus, which encodes an Ets family transcription factor, is frequently rearranged in human leukemias of myeloid or lymphoid origins. By gene targeting in mice, we previously showed that TEL-/- mice are embryonic lethal because of a yolk sac angiogenic defect. TEL also appears essential for the survival of selected neural and mesenchymal populations within the embryo proper. Here, we have generated mouse chimeras with TEL-/- ES cells to examine a possible requirement in adult hematopoiesis. Although not required for the intrinsic proliferation and/or differentiation of adult-type hematopoietic lineages in the yolk sac and fetal liver, TEL function is essential for the establishment of hematopoiesis of all lineages in the bone marrow. This defect is manifest within the first week of postnatal life. Our data pinpoint a critical role for TEL in the normal transition of hematopoietic activity from fetal liver to bone marrow. This might reflect an inability of TEL-/- hematopoietic stem cells or progenitors to migrate or home to the bone marrow or, more likely, the failure of these cells to respond appropriately and/or survive within the bone marrow microenvironment. These data establish TEL as the first transcription factor required specifically for hematopoiesis within the bone marrow, as opposed to other sites of hematopoietic activity during development.

278 citations


Journal ArticleDOI
15 Dec 1998-Blood
TL;DR: The TEL/AML1 fusion was identified in only 1 of 32 analyzable relapsed ALL patients, in concordance with previous reports of improved disease-free survival in TEL or AML1-positive patients, and support the need for prospective analysis of prognosis in Tel/AMl1- positive patients.

124 citations


Book ChapterDOI
01 Jan 1998
TL;DR: The authors' data narrow down regions on chromosomes 6q, 9p, l lq and 12p containing putative tumor suppressor genes which may play an important role in leukemogenesis of childhood ALL.
Abstract: Chromosomal abnormalities on 6q, 9p, 11q and 12p have been reported frequently in acute lymphoblastic leukemia (ALL). In order to define regions that may contain tumor suppressor genes more precisely, the loss of heterozygosity (LOH) was analyzed on respective chromosome arms in childhood ALL. Using highly informative microsatellite markers, LOH was found in 17 of 112 (15%) ALL samples on 6q; in 29 of 54 (54%) on 9p; in 14 of 112 cases (13%) on 11q; in 33 of 100 (33%) on 12p. The commonly deleted region on 6q was flanked by the markers D6S468 and D6S283/D6S449 at 6q21. In 27 of the 29 cases with LOH on 9p the critical region was characterized by D9S1747 and D9S1748. Homozygous deletions of the CDKN2/INK4A/p16 gene residing in this region were found in 14 of the 27 patients. Two cases revealed LOH at the IFNA locus. Two distinct commonly deleted regions were identified on 11q and 12p, respectively. One region at 11g22 was flanked by D11S901 and D11S1391, and the other at 11q23 by D11S614 and D11S924. On chromosome 12p, one critical region was flanked by the markers D12S77 and D12S98 including the TEL gene, and the other was localized around the p27/kipl locus. Our data narrow down regions on chromosomes 6q, 9p, l lq and 12p containing putative tumor suppressor genes which may play an important role in leukemogenesis of childhood ALL.

1 citations