Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

VSV-G-pseudotyped lentiviral vectors expressing p16(INK4a) or p14(ARF) were used to infect at high-efficiency Philadelphia chromosome (Ph)-positive leukemia cell lines lacking endogenous transcripts. Restoration of p16(INK4a) accumulated cells in the G0/G1 phase of cell cycle and restoration of p14(ARF) induced their apoptosis, followed by significant growth inhibition. Transduction of primary blast cells from chronic myeloid leukemia in blast crisis (CML-BC) and Ph-positive acute lymphoblastic leukemia (ALL) with p16(INK4a) or p14(ARF) virus also resulted in cell growth inhibition and/or apoptosis with a patient-to-patient variation, whereas clonal growth and differentiation of cord blood progenitor cells were not affected by enforced expression of INK4a/ARF. Furthermore, upon viral transduction at low multiplicity of infection, INK4a/ARF potentiated the effect of imatinib mesylate on Ph-positive leukemia cell lines in an additive but not synergistic manner. These results suggest that INK4a/ARF protein-mimetic agents may be promising options for Ph-positive leukemias in combination with imatinib mesylate.
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PMID:Restoration of INK4a/ARF gene inhibits cell growth and cooperates with imatinib mesylate in Philadelphia chromosome-positive leukemias. 2433 Aug 49

Aberrant DNA methylation of tumor suppressor genes has been reported in all major types of leukemia with potential involvement in the inactivation of regulatory cell cycle and apoptosis genes. However, most of the previous reports did not show the extent of concurrent methylation of multiple genes in the four leukemia types. Here, we analyzed six key genes (p14, p15, p16, p53, DAPK and TMS1) for DNA methylation using methylation specific PCR to analyze peripheral blood of 78 leukemia patients (24 CML, 25 CLL, 12 AML, and 17 ALL) and 24 healthy volunteers. In CML, methylation was detected for p15 (11%), p16 (9%), p53 (23%) and DAPK (23%), in CLL, p14 (25%), p15 (19%), p16 (12%), p53 (17%) and DAPK (36%), in AML, p14 (8%), p15 (45%), p53 (9%) and DAPK (17%) and in ALL, p15 (14%), p16 (8%), and p53 (8%). This study highlighted an essential role of DAPK methylation in chronic leukemia in contrast to p15 methylation in the acute cases, whereas TMS1 hypermethylation was absent in all cases. Furthermore, hypermethylation of multiple genes per patient was observed, with obvious selectiveness in the 9p21 chromosomal region genes (p14, p15 and p16). Interestingly, methylation of p15 increased the risk of methylation in p53, and vice versa, by five folds (p=0.03) indicating possible synergistic epigenetic disruption of different phases of the cell cycle or between the cell cycle and apoptosis. The investigation of multiple relationships between methylated genes might shed light on tumor specific inactivation of the cell cycle and apoptotic pathways.
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PMID:DNA hypermethylation of cell cycle (p15 and p16) and apoptotic (p14, p53, DAPK and TMS1) genes in peripheral blood of leukemia patients. 2452 84

It is generally accepted that the short arm of chromosome 6 is a likely site to be involved in chromosomal rearrangements of MDS/ANLL following radio/chemotherapy. We report here two cases of t(3;6)(p14;p22). One patient is a 55 years old male with a previous history of occupational exposure who developed, an acute megakaryoblastic leukemia after a preleukemic phase. Chromosome analysis showed a t(3;6)(p14;p22), associated with del (5)(q14q31), -7, with variations and a trend to hypoploidy. The second patient is a 33 years old man, with chronic myeloid leukemia treated with Hydroxyurea (HU), HU + $aL-IFN and $aL-IFN alone. The first cytogenetic study before treatment, showed a t(9;22)(q34;q11). In the following months the patient had simultaneously t(9;22)(q34;q11) + t(3;6)(p14;p22) in a minority and thereafter in all the mitoses, with progressive deterioration, megakaryocyte abnormalities, but no blast crisis. Our patients are compared with the only 5 other published cases with t(3;6)(p14;p22), who shared some common features, namely a past history of chemo/radiotherapy or exposure to chemical mutagens and an association with other, so-called "secondary" chromosome aberrations, on segments 3p, 5q, 7q, 12p and 17p. We suggest that this uncommon translocation t(3;6) is nonrandom. It is worth noting that band 6p21 is the site of pim 1 oncogen, and that a fragile site is located on band 3p14.
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PMID:Two Cases of Translocation t(3;6)(p14;p22): A Non Random Chromosomal Abnormality? 2746 55


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