Deletions of Interferon Genes in Acute Lymphoblastic Leukemia

Abstract

Structural rearrangements involving the short arm of chromosome 9, including bands 9p21 and 22, are found in the leukemia cells of 7 to 13 percent of patients with acute lymphoblastic leukemia. The interferon-alpha gene cluster and the interferon-beta 1 gene have been localized to this chromosomal region. We have previously demonstrated deletions of these genes in several cell lines established in vitro from patients with lymphoblastic leukemia. We report here homozygous or hemizygous deletions of the interferon-alpha and interferon-beta 1 genes in samples of leukemia cells from patients with lymphoblastic leukemia. Of 62 patients examined, 18 (29 percent) had such deletions. Four patients (7 percent) had homozygous deletions of the interferon-alpha gene cluster; of these, one also had a homozygous deletion and three had hemizygous deletions of the interferon-beta 1 gene. Fourteen patients (23 percent) had hemizygous deletions of both the interferon-alpha gene cluster and the interferon-beta 1 gene. In 8 of the 18 patients with deletions, the deletions of interferon genes were submicroscopic; in the 11 other patients, chromosomal rearrangements of 9p, including translocations or deletions, were visible on light microscopy. These chromosomal and molecular deletions are likely to be related to the loss of a tumor-suppressor gene (or genes) located on 9p, which may be an interferon gene or an unrelated but closely linked gene.

Recurrent DNA copy number changes in 1q, 4q, 6q, 9p, 13q, 14q and 22q detected by comparative genomic hybridization in malignant mesothelioma

“…Homozygous deletions of chromosome 9p2i-p22 have been detected in various tumour types including leukaemia, mesothelioma, melanoma, bladder carcinomas, lung cancer and renal cell carcinoma (Diaz et al, 1990;Fountain et al, 1992;Cairns et al, 1993;Cheng et al, 1993;Mead et al, 1994). Recently, two putative tumour-suppressor genes p16 (MTS1) and p15 (MTS2), both encoding cyclin-dependent kinase 4 (CDK4) inhibitors, have been mapped to the short arm of chromosome 9 (p21) (Kamb et al, 1994).…”

Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human leukemia–lymphoma cells

“…4 The observation that the human chromosome 9p21 region is a frequent site of deletions and rearrangements in many tumor types including leukemias 5 implied the existence of a tumor suppressor gene within 9p21 which is involved in tumor formation. The type-I interferon gene cluster maps to 9p21-22 and was originally suggested as the target for deletions in leukemias, 6 but was instead later considered to be an innocent bystander being deleted because of its close genomic proximity to other genes. 7 Later, the gene p16 INK4A was identified in this region and was found to possess many features suggesting that it is a gene relevant to loss of heterozygosity at this site.…”

Alterations of p16 and p15 genes in acute leukemia with MLL gene rearrangements and their correlation with clinical features

“…[1][2][3] The p16 gene (also referred to as MTS1, INK4A, CDK4I or CDKN2) and p15 gene (also referred to as MTS2 or INK4B), which share extensive nucleotide sequence homology and are closely linked on 9p21, have been suggested to be new tumor suppressor genes by several investigators. The proteins encoded by p16 and p15 are key factors in the negative control of cell proliferation in that they inhibit the activity of two cyclindependent kinases (CDKs), CDK4 and CDK6.…”