Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Enzyme
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Query: EC:2.7.7.49 (
reverse transcriptase
)
31,746
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Particles with the density and enzymatic activity characteristic of known oncornavirus have been previously described in bone marrow cells from patients with leukemia in relapse and in remission. We have confirmed these findings and studied two patients in whom
preleukemia
was among the diagnostic considerations. Following cultivation of bone marrow from these patients for 1 week in conditioned media with dexamethasone, a high-speed pellet of the supernatant fluid and disrupted cells was prepared and analyzed on a sucrose gradient for enzymatic activity characteristic of
RNA-directed DNA polymerase
(
reverse transcriptase
). Peaks of endogenous DNA polymerase activity showing ribonuclease sensitivity and/or stimulation with the synthetic template poly(rC)-(dG)12-18 were demonstrated in both patients at densities of 1.15 to 1.19 and 1.21 to 1.24 g/ml. Subsequently, diagnosis 2 and 4 months after initial evaluation revealed acute myelogenous leukemia and malignant histiocytosis, respectively. Prior studies have suggested a possible etiological significance of such particles in human leukemia. The demonstration of similar particles preceding clinically overt disease in these patients supports this hypothesis and offers the possibility of early diagnosis and treatment.
...
PMID:Oncornavirus-like particles from cultured bone marrow cells preceding leukemia and malignant histiocytosis. 5 58
In a group of 44 patients with primary and secondary aplastic anemia, four (9%) developed an acute leukemia. Cytological changes that pointed to a
preleukemia
were not observed during the preleukemic stage. The possibility is discussed whether a aplastic anemia and a
preleukemia
can be distinguished by cytological, cytochemical and cytogenetic tests, by agar-culture technique, liquid-culture and determination of
reverse transcriptase
.
...
PMID:[Aplastic anemia-a preleukemic stage (author's transl)]. 119 58
We have isolated a lymphoid cell line,
MDS
, from the pleural exudate of a patient with chronic myelomonocytic leukemia. The cells are biphenotypic, containing various T-cell and myeloid markers, and are surface negative for CD4 and CD8 but have low CD4 mRNA. The cells grow in suspension with a doubling time of 15 hr, have been karyotyped as trisomy 21, are negative for human immunodeficiency virus type 1 (HIV-1), and are tumorigenic in the nude mouse. We have isolated two stable HIV-1-producing cell lines,
MDS
-T, by transfecting
MDS
cells with pHXBc2, and
MDS
-I, by infecting
MDS
cells with HIV-1IIIB. In 24 hr, 1 x 10(5)
MDS
-T or
MDS
-I cells produce 46 ng of p24 per ml and
reverse transcriptase
that is capable of incorporating 0.2 pmol of [32P]TTP into oligo(dT).poly(A). Ultrastructural studies showed numerous mature viral particles in
MDS
-T and
MDS
-I cells that are capable of infecting T cells. HIV-1 infection could be inhibited by 25% in the
MDS
cells with the anti-CD4 antibody Leu 3a. For over a year
MDS
-T and
MDS
-I cells have been producing high concentrations of HIV-1 in culture. A subclone derived from the
MDS
cells behaves like the parent cells when transfected or infected with HIV-1. In contrast to other T-cell lines, neither phorbol 12-myristate 13-acetate nor tumor necrosis factor alpha stimulated the replication of HIV-1, whereas bromoadenosine 3',5'-cyclic monophosphate or interferon alpha caused 50% and 80% inhibition of
reverse transcriptase
production, respectively. These chronically infected T-cell lines are a useful model system to study the effect of anti-HIV agents and cellular factors required for HIV-1 replication.
...
PMID:Productive nonlytic human immunodeficiency virus type 1 replication in a newly established human leukemia cell line. 143 50
Infection due to the human immunodeficiency virus (HIV) has been complicated by the development of acute nonlymphocytic leukemia in five patients whose cases have previously been reported; other manifestations, including
preleukemia
, myelofibrosis, and myeloid hyperplasia, have also been reported in patients infected with HIV. We report the sixth case of an HIV-infected patient who developed acute myelomonocytic leukemia; HIV infection was documented by tests for serum antibodies (enzyme-linked immunosorbent assay and western blotting), by a markedly elevated p24 antigen level in plasma, and by cultures of CSF and peripheral blood that were positive for HIV. Furthermore, myelomonoblasts that were cultured without the addition of growth factors displayed evidence of HIV replication through the presence of p24 antigen and
reverse transcriptase
activity, both of which lasted for 4 weeks in the supernatant fluid of the cell cultures. This case report provides the first data indicating that HIV may infect myelomonoblasts in vivo and represents the sixth reported case of an association between HIV infection and pure acute nonlymphocytic leukemia.
...
PMID:Relationship between acute myelomonoblastic leukemia and infection due to human immunodeficiency virus. 190 61
Chronic myelogenous leukemia (CML) is a stem cell disease which, on a clinical level, progresses from the release from growth control of normally differentiated cells (a preleukemic state) to an acute leukemia. On a molecular level, the evolution of CML to acute leukemia is a multistep process. We propose that an early step, at the stem cell level, is acquisition of the ability for gene movement, which allows subsequent submicroscopic and chromosomal rearrangements that cause changes in the growth characteristics and regulation of the stem cell. A specific platelet DNA polymerase (PDP -
reverse transcriptase
) may play a role in gene movement. The characteristic reciprocal translocation of chromosomes #9 and #22, causing the activation of the c-abl oncogene, appears to be responsible for the uncontrolled cellular growth. Yet, other growth factors (e.g., platelet derived growth factor) and activated oncogenes (e.g., c-sis) must be responsible for the stimulation, progression, and variability seen during the course of the disease. Because CML is a progressive disease with clinically definable stages, CML appears to be a model system for the study of the molecular basis of the progression of
preleukemia
to leukemia specifically, and preneoplasia to aggressive neoplasia in general.
...
PMID:Implications of retroviral and oncogene activity in chronic myelogenous leukemia. 243 4
Variants of the t(15;17)(q22;q12-q21) chromosomal rearrangement associated with acute promyelocytic leukemia (APL) have been previously described and they frequently involve either chromosome 15 and/or 17. Previously we reported a rare variant t(11;17). We now describe two patients with
myelodysplastic syndrome
(
MDS
) that transformed to APL-like leukemia. Both had trisomy 11 at the diagnosis of APL-like leukemia. Following treatment for APL, patient 1 reverted to
MDS
and showed a normal karyotype. When leukemia recurred, his bone marrow karyotype was 47,XY,t(4;11), +11,der(22)t(1;22). Both patients were treated with all-trans retinoic acid (ATRA) for APL for 5 weeks, but failed to respond. The karyotype of patient 1 after ATRA treatment was 46,XY,t(4;11); the trisomy 11 had been lost and the bone marrow was replaced with immature myeloblasts without promyelocytes. In patient 2, the karyotype remained the same as at diagnosis, i.e., 47,X,-Y,dir ins(4;7),del(5), +6,del(7), +8, + 11,-18. Molecular analysis by
reverse transcriptase
PCR analysis showed the presence of wild type retinoic acid receptor alpha (RARA) and the absence of the PML-RARA chimeric gene associated with t(15;17). Additional analysis of PLZF, a new zinc finger gene associated with t(11;17), also showed the absence of this hybrid gene. These data support the concept that APL is a heterogeneous disorder and that variants with chromosome 11 rearrangement exist that do not respond to ATRA.
...
PMID:Myelodysplastic syndrome transforming to acute promyelocytic-like leukemia with trisomy and rearrangement of chromosome 11. 751 69
The t(8;21) is a frequent chromosome abnormality in acute myeloid leukemia (AML), particularly associated with M2 of the French-American-British (FAB) classification, but also found in a few patients with
myelodysplastic syndrome
(
MDS
). The two genes involved in the t(8;21) have been recently isolated and the cDNA of the AML1/ETO fusion gene identified. We have investigated a series of AML and
MDS
patients by a
reverse transcriptase
-polymerase chain reaction (RT-PCR) and analyzed the clinical and laboratory features of leukemia with t(8;21). The t(8;21) was only found in a subset of M2, which had the clinical and hematological features distinct from those M2 without t(8;21). M2 with t(8;21) was associated with a significantly higher myeloid differentiation and with a good response to chemotherapy. Moreover, among the patients with refractory anemia with excess of blasts in transformation (RAEB-T) the t(8;21) was also significantly associated with a higher myeloid differentiation and a good response to chemotherapy. M2 patients with t(8;21) could be distinguished on a number of hematological parameters, eg white blood cell count and percentage of bone marrow myeloblasts and promyelocytes, from RAEB-T carrying the t(8;21). Based on these findings we suggest that leukemia patients carrying t(8;21) can be grouped into two types; overt acute myeloid leukemia (M2) and smoldering or slowly evolving myeloid leukemia.
...
PMID:High degree of myeloid differentiation and granulocytosis is associated with t(8;21) smoldering leukemia. 763 Jan 88
Inactivation of the deleted in colorectal carcinoma (DCC) tumor suppressor gene has been reported not only in colorectal carcinoma but also in other human malignancies. In order to evaluate the role of the DCC gene in leukemogenesis, we examined DCC expression using the
reverse transcriptase
-polymerase chain reaction (RT-PCR) method. Expression of the DCC gene was reduced or absent in 10 of 39 (26%) patients with acute myelogenous leukemia (AML), three of 14 (29%) patients with acute lymphocytic leukemia (ALL), seven of 33 (21%) patients with chronic myelogenous leukemia (CML), three of 39 (8%) patients with
myelodysplastic syndromes
(
MDS
), and five of nine (56%) patients with overt leukemia progressed from
MDS
. These findings suggest that inactivation of the DCC gene contributes to some instances of leukemogenesis.
...
PMID:Expression of the DCC gene in human hematological malignancies. 769 19
We investigated expression of the human ecotropic virus integration site-1 (EVI1) gene in patients with leukemia and
myelodysplastic syndrome
(
MDS
) using the
reverse transcriptase
-polymerase chain reaction (RT-PCR) method. The EVI1 transcripts were detected in 5 (10.0%) of 50 patients with de novo acute myeloid leukemia (AML), including two AML patients with trilineage
myelodysplasia
, and in 8 (34.8%) of 23 patients with post-
myelodysplastic syndrome
AML (post-
MDS
AML). EVI1 expression was also detected in 6 (35.3%) of 17
MDS
patients and three of six patients with chronic myeloid leukemia (CML) in myelomegakaryoblast crisis. No EVI1 transcripts were detected in patients with acute lymphoid leukemia (n = 15) or CML in lymphoid blast crisis (n = 4). Chromosomal abnormalities at the 3q26 region, where the EVI1 gene is located, were found in one patient with
MDS
and two patients with CML myelomegakaryoblast crisis who had EVI1 expression. Our results showed that EVI1 expression was frequent in patients with post-
MDS
AML and AML with trilineage
myelodysplasia
, regardless of the presence or absence of 3q26 abnormalities. EVI1 expression was accompanied by expression of GATA-1 and GATA-2, and often by stem cell leukemia (SCL) gene expression. In patients with post-
MDS
AML, EVI1 expression was not always associated with a 3q26 abnormality, whereas EVI1 expression in CML myelomegakaryoblast crisis was often linked to a 3q26 abnormality. Our results suggest that the leukemogenic role of EVI1 expression may differ between post-
MDS
AML and leukemia, with EVI1 expression associated with a 3q26 abnormality.
...
PMID:Ecotropic virus integration site-1 gene preferentially expressed in post-myelodysplasia acute myeloid leukemia: possible association with GATA-1, GATA-2, and stem cell leukemia gene expression. 778 Jan 55
To evaluate the molecular events in the genome that are associated with
myelodysplastic syndromes
(
MDS
) and the development of leukemia, we investigated the expression of the deleted in colorectal carcinoma (DCC) gene by the
reverse transcriptase
-polymerase chain reaction (RTPCR) method in 24
MDS
cases and in 7 overt leukemia cases that progressed from
MDS
. Expression of the DCC gene was absent or extremely reduced in 2 of the 24
MDS
cases, and those 2 cases developed overt leukemia within 6 months. Moreover, in 5 of the 7 cases of overt leukemia that developed from
MDS
, expression of the DCC gene was absent or extremely reduced. These findings suggest that inactivation of the DCC gene may be the late event that triggers the progression of
MDS
to leukemia.
...
PMID:Expression of the DCC gene in myelodysplastic syndromes and overt leukemia. 837 79
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