TY - JOUR
T1 - Deletion of 5q in myeloid leukemia cells HL-60
T2 - An L1 element-mediated instability
AU - Hejlik, Daniel P.
AU - Nagarajan, Lalitha
N1 - Funding Information:
We thank Dr. Emil J. Freireich for the paraffin blocks from patient HL-60, Dr. Maxine Singer for valuable comments on the manuscript, and Dr. Kay Huebner for helpful discussions during the initial stages of this work. We also thank Dr. Hong Liang for suggestions on the PCR of archived material. These studies were supported by PHS grant CA66982 to L.N. The University of Texas M.D. Anderson Cancer Center DNA sequencing facility is supported by core grant CA16672.
PY - 2005/1/15
Y1 - 2005/1/15
N2 - Complete and partial deletions of chromosome 5 are recurrent anomalies associated with refractory myelogenous leukemia. Recent evidence suggests that these deletions arise from unbalanced two- or three-way translocations, rather than from interstitial breaks or segregation errors; however, very little is known about the molecular mechanisms underlying this multistep genomic instability. We have analyzed a complex rearrangement of chromosome band 5q both in the primary leukemic cells of the patient from whom the acute myelogenous leukemia (AML) cell line HL-60 was derived and in the HL-60 cells in culture. This highly stable rearrangement is a product of multiple events in which a small single-copy fragment flanking the 3′ end of the GMCSF gene is juxtaposed to novel L1Hs sequences. The resulting genomic fragment is found inserted into a telomeric locus (D5S89), with loss of 4.1 Mbp of in-between sequences, encoding one or more candidate myeloid leukemia suppressor genes. The findings are consistent with a dynamic role for L1Hs in mediating instability that results in a complex chromosomal rearrangement. Furthermore, we provide what may be the first example of multiple L1Hs-associated deletions involving both a growth factor gene and a tumor suppressor locus in a primary leukemic clone.
AB - Complete and partial deletions of chromosome 5 are recurrent anomalies associated with refractory myelogenous leukemia. Recent evidence suggests that these deletions arise from unbalanced two- or three-way translocations, rather than from interstitial breaks or segregation errors; however, very little is known about the molecular mechanisms underlying this multistep genomic instability. We have analyzed a complex rearrangement of chromosome band 5q both in the primary leukemic cells of the patient from whom the acute myelogenous leukemia (AML) cell line HL-60 was derived and in the HL-60 cells in culture. This highly stable rearrangement is a product of multiple events in which a small single-copy fragment flanking the 3′ end of the GMCSF gene is juxtaposed to novel L1Hs sequences. The resulting genomic fragment is found inserted into a telomeric locus (D5S89), with loss of 4.1 Mbp of in-between sequences, encoding one or more candidate myeloid leukemia suppressor genes. The findings are consistent with a dynamic role for L1Hs in mediating instability that results in a complex chromosomal rearrangement. Furthermore, we provide what may be the first example of multiple L1Hs-associated deletions involving both a growth factor gene and a tumor suppressor locus in a primary leukemic clone.
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U2 - 10.1016/j.cancergencyto.2004.05.011
DO - 10.1016/j.cancergencyto.2004.05.011
M3 - Article
C2 - 15642388
AN - SCOPUS:11844259481
SN - 0165-4608
VL - 156
SP - 97
EP - 103
JO - Cancer Genetics and Cytogenetics
JF - Cancer Genetics and Cytogenetics
IS - 2
ER -