Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytologic and cytogenetic results obtained from patients fulfilling the FAB criteria for the diagnosis of acute nonlymphocytic leukemia (ANLL) of megakaryocytic lineage (ANLL-M7) are reported. Eleven cases were de novo ANLL-M7, of whom three presented with acute myelofibrosis. Four cases were megakaryoblastic transformations of chronic myelogenous leukemia (two cases), refractory anemia with excess of blasts (one case), and polycythemia vera (one case). Four patients showed a minority of granular blasts, with occasional Auer rods in one. Positive myeloperoxidase and/or sudan black-B stainings and CD13 positivity in these cases were consistent with the presence of a myeloid involvement. Morphologic evidence of associated myelodysplastic features was detected in all evaluable patients with de novo ANLL-M7. These cytologic findings indicate that ANLL-M7 may frequently represent a multilineage proliferation. Cytogenetic studies revealed -7/7q- and +8, alone or in combination with additional aberrations, in three cases each. Rearrangements involving bands 3q21 or 3q26 were seen in two patients and +21, as an additional aberration, in one. Other structural rearrangements all observed in a single patient were inv(16)(p13q22) at megakaryoblastic relapse with bone marrow eosinophilia, t(13;20)(q13 or 14;q11), del(20)(q11), and der(7)t(7;17)(p14;q22). Most breakpoints of these aberrations are located at bands frequently rearranged in malignant myeloid stem cell disorders. A review of 31 cases of the literature showed a frequent occurrence of -7/7q- and -5/5q- in ANLL-M7. Many of the chromosome aberrations so far described in ANLL-M7 appear to be shared by a spectrum of myeloid neoplasias and may be related to mechanisms conferring proliferative advantage to undifferentiated stem cells.
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PMID:Multipotent stem cell involvement in megakaryoblastic leukemia: cytologic and cytogenetic evidence in 15 patients. 279 Feb 2

The retinoblastoma (Rb), cyclin-dependent kinase (CDK), and CDK inhibitor genes regulate cell generation, and deregulation can produce increased cell growth and tumorigenesis. Polycythemia vera (PV) is a clonal myeloproliferative disease where the mechanism producing increased hematopoiesis is still unknown. To investigate possible defects in cell-cycle regulation in PV, the expression of Rb and CDK inhibitor gene messenger RNAs (mRNAs) in highly purified human erythroid colony-forming cells (ECFCs) was screened using an RNase protection assay (RPA) and 11 gene probes. It was found that RNA representing exon 2 of p16(INK4a) and p14(ARF) was enhanced by 2.8- to 15.9-fold in 11 patients with PV. No increase of exon 2 mRNA was evident in the T cells of patients with PV, or in the ECFCs and T cells from patients with secondary polycythemia. p27 also had elevated mRNA expression in PV ECFCs, but to a lesser degree. Because the INK4a/ARF locus encodes 2 tumor suppressors, p16(INK4a) and p14(ARF) with the same exon 2 sequence, the increased mRNA fragment could represent either one. To clarify this, mRNA representing the unique first exons of INK4a and ARF were analyzed by semiquantitative reverse transcription-polymerase chain reaction. This demonstrated that mRNAs from the first exons of both genes were increased in erythroid and granulocyte-macrophage cells and Western blot analysis showed that the INK4a protein (p16(INK4a)) was increased in PV ECFCs. Sequencing revealed no mutations of INK4a or ARF in 10 patients with PV. p16(INK4a) is an important negative cell-cycle regulator, but in contrast with a wide range of malignancies where inactivation of the INK4a gene is one of the most common carcinogenetic events, in PV p16( INK4a) expression was dramatically increased without a significant change in ECFC cell cycle compared with normal ECFCs. It is quite likely that p16(INK4a) and p14(ARF) are not the pathogenetic cause of PV, but instead represent a cellular response to an abnormality of a downstream regulator of proliferation such as cyclin D, CDK4/CDK6, Rb, or E2F. Further work to delineate the function of these genes in PV is in progress. (Blood. 2001;97:3424-3432)
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PMID:Increased expression of the INK4a/ARF locus in polycythemia vera. 1136 33