Deletion of 5q in myeloid leukemia cells HL-60: an L1 element-mediated instability.
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.
Hejlik
Daniel P
DP
Department of Molecular Genetics, The University of Texas, Box 45, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Nagarajan
Lalitha
L
D001483:Base Sequence; D043171:Chromosomal Instability / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003001:Cloning, Molecular; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D018922:HL-60 Cells; D006801:Humans; D008969:Molecular Sequence Data; D015183:Restriction Mapping
D016178:Granulocyte-Macrophage Colony-Stimulating Factor