Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current progressive chemotherapy and transplantation induce not only remission but complete cure. By this reason, the detecting system for MRD must be established in complete remission phase. In this study, we showed the detecting for MRD by molecular biology techniques in the patients with non-Hodgkin's lymphoma, CML, B-ALL and AML. 1) Malignant cells could be detected in peripheral blood or bone marrow cells by Southern blot analysis in 15 of 30 patients with non-Hodgkin's lymphoma. 2) In CML patients, BCR/ABL fusion gene was positive by RT-PCR for 6 months after BMT, 4 patients became undetectable for 7 months after BMT. 3) Rearrangement of Ig H has been disappeared in 12 months after achieved complete remission the patients with B-ALL. In conclusion, the detection for MRD remain an important goal for therapy including chemotherapy and bone marrow transplantation in hematopoetic malignancy.
 ...
PMID:[Detection of residual malignant cells in patients with hematopoietic malignancy]. 831 24

Interleukin-11 (IL-11) is a pleiotropic cytokine with effects on many different targets. Within the hematopoietic system, the effects of IL-11 are largely manifest only through combination with other cytokines, including IL-3 and Steel factor (SF). In the present study, we addressed the question of IL-11 responsiveness within the different types of human leukemic cells, as well as the mechanism of action of IL-11 at the cellular level. Analysis of a panel of samples from different patients with acute myeloblastic leukemia (AML) and myeloid leukemic cell lines indicated that IL-11 alone was ineffective in supporting myeloid leukemic cell growth but frequently enhanced growth supported by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or SF. In contrast, three acute pre-B lymphocytic leukemia (pre-B-ALL) and two acute T lymphocytic leukemia (T-ALL) lines failed to respond to IL-11 alone or when combined with other cytokines. The growth enhancement of IL-11 among the AML patient samples was dose dependent and remarkably constant with half-efficient concentrations in the range of 0.3 to 0.4 ng/mL. The thymidine suicide studies with the patient samples revealed that 40% to 50% of the blast cells were in S-phase when exposed for 16 hours to IL-3 and this level was increased to 70% to 90% in response to either IL-11 or IL-6. Our data suggest that the latter two interleukins act synergistically with the direct mitogenic factor, IL-3, in triggering AML blast-cell proliferation. Detailed analysis with several patient samples further revealed that SF and IL-11 both enhance IL-3-supported clonogenic growth of AML blasts and the combination of all three growth factors yields optimal growth. In contrast, IL-6 does not further enhance the effect of IL-11. These results indicate that SF and IL-11 enhance IL-3-dependent clonogenic growth through two distinct pathways, whereas IL-6 and IL-11 may trigger the same pathway.
 ...
PMID:Effects of interleukin-11 on the proliferation and cell cycle status of myeloid leukemic cells. 845 5

Three patients with secondary acute leukaemia after treatment with topoisomerase II inhibitor agents are described. Two patients had acute myeloid leukaemia (AML). FAB M5a, one had pro-B-acute lymphoblastic leukaemia (ALL). The interval between initiation of chemotherapy and the onset of secondary acute leukaemia was 19-20 months. 11q23 rearrangements were detected in all cases. They were due to translocations t(11;19) (q23;p13.3), t(11;16)(q23;p13) and t(4;11)(q21;q23), respectively. Fluorescence in situ hybridization (FISH) with Yeast Artificial Chromosome (YAC) probe 13HH4 spanning the ALL-1 gene on 11q23 confirmed that in each case the ALL-1 gene had been disrupted by the translocations. The study underlined the relationship between the development of secondary acute leukaemias with 11q23 rearrangement and previous chemotherapy with topisomerase II inhibitor agents. So far, however, only six adult patients with secondary ALL with t(4;11) after treatment with topoisomerase II inhibitor agents have been reported. All with t(4;11) mostly occurs in infants or young children. Our patient received epirubicin continuously for >19 months. This indicates that both myeloid and lymphoid leukaemias with involvement of the ALL-1 gene can be induced by exogenous agents, especially topoisomerase II inhibitors. Thus they may have a common biological background. This hypothesis was substantiated by means of combined immunophenotyping and FISH (FICTION). In the case of AML M5a with t(11;19), the tumour cells with ALL-1 rearrangement expressed CD34. Moreover, the pro-B-ALL with t(4;11) was CD34 positive. These findings suggest that the cell of origin of secondary AML and ALL with 11q23 rearrangement is an immature haemopoietic progenitor cell.
 ...
PMID:Secondary acute leukaemias with 11q23 rearrangement: clinical, cytogenetic, FISH and FICTION studies. 861 34

The novel hematopoietic growth factor FLT3 ligand (FL) is the cognate ligand for the FLT3, tyrosine kinase receptor (R), also referred to as FLK-2 and STK-1. The FLT3R belongs to a family of receptor tyrosine kinases involved in hematopoiesis that also includes KIT, the receptor for SCF (stem cell factor), and FMS. the receptor for M-CSF (macrophage colony- stimulating factor). Restricted FLT3R expression was seen on human and murine hematopoietic progenitor cells. In functional assays recombinant FL stimulated the proliferation and colony formation of human hematopoietic progenitor cells, i.e. CD34+ cord and peripheral blood, bone marrow and fetal liver cells. Synergy was reported for co-stimulation with G-CSF (granulocyte-CSF). GM-CSF (granulocyte-macrophage CSF), M-CSF, interleukin-3 (IL-3), PIXY-321 (an IL-3/GM-CSF fusion protein) and SCF. In the mouse, FL potently enhanced growth of various types of progenitor/precursor cells in synergy with G-CSF, GM-CSF, M-CSF, IL-3, IL-6, IL-7, IL-11, IL-12 and SCF. The well-documented involvement of this ligand-receptor pair in physiological hematopoiesis brought forth the question whether FLT3R and FL might also have a role in the pathobiology of leukemia. At the mRNA level FLT3R was expressed by most (80-100%) cases of AML (acute myeloid leukemia) throughout the different morphological subtypes (MO-M7), of ALL(acute lymphoblastic leukemia) of the immunological subtypes T-ALL and BCP-ALL (B cell precursor ALL including pre-pre B-ALL, cALL and pre B-ALL), of AMLL (acute mixed-lineage leukemia), and of CML (chronic myeloid leukemia) in lymphoid or mixed blast crisis. Analysis of cell surface expression of FLT3R by flow cytometry confirmed these observations for AML (66% positivity when the data from all studies are combined), BCP-ALL (64%) and CML lymphoid blast crisis (86%) whereas less than 30% of T-ALL were FLT3R+. The myeloid, monocytic and pre B cell type categories also contained the highest proportions of FLT3R+ leukemia cell lines . In contrast to the selective expression of the receptor, FL expression was detected in 90-100% of the various cell types of leukemia cell lines from all hematopoietic cell lineages. The potential of FL to induce proliferation of leukemia cells in vitro was also examined in primary and continuously cultured leukemia cells. The data on FL-stimulated leukemia cell growth underline the extensive heterogeneity of primary AML and ALL samples in terms of cytokine-inducible DNA synthesis that has been seen with other effective cytokines. While the majority of T-ALL (0-33% of the cases responded proliferatively; mean 11%) and BCP-ALL (0-30%; mean 20%) failed to proliferate in the presence of FL despite strong expression of surface FLT3R, FL caused a proliferative response in a significantly higher percentage of AML cases (22-90%; mean 53%). In the panel of leukemia cell lines examined only myeloid and monocytic growth factor- dependent cell lines increased their proliferation upon incubation with FL, whereas all growth factor-independent cell lines were refractory to stimulation. Combinations of FL with G-CSF, GM-CSF, M-CSF, IL-3, PIXY- 321 or SCF and FL with IL-3 or IL-7 had synergistic or additive mitogenic effects on primary AML and ALL cells, respectively. The potent stimulation of the myelomonocytic cell lines was further augmented by addition of bFGF (basic fibroblast growth factor), GM-CSF, IL-3 or SCF. The inhibitory effects of TGF-beta 1 (transforming growth factor-beta 1) on FL- supported proliferation were abrogated by bFGF. Taken together, these results demonstrate the expression of functional FLT3R capable of mediating FL- dependent mitogenic signaling in a subset of AML and ALL cases further underline the heterogeneity of AML and ALL samples in their proliferative response to cytokine.
 ...
PMID:Expression of FLT3 receptor and response to FLT3 ligand by leukemic cells. 861 33

We have studied the molecular characteristics of the T cell receptor (TcR) genes in 16 patients with CD7+ early T cell acute lymphoblastic leukemia (T-ALL), defined as being positive for CD7 but negative for CD3/4/8, myeloperoxidase (MPO), and CD19/20. Using gene analysis, rearrangement was demonstrated in one patient for immunoglobulin heavy chain (IgH) gene, five for TcR-beta gene, and four for TcR-gamma gene. Fifteen patients (94%) had rearranged band(s) involving the joining region of the TcR-delta chain gene. In nine cases these were the only rearrangements, whereas in six cases TcR-beta and/or TcR-gamma gene rearrangements were found as well. The D delta 2(D delta)J delta 1 rearrangement was demonstrated in 87.5% (14/16) of cases. D delta 2(D delta)J delta 3 was recognized in one patient, D delta 2D delta 3 was found in three, and V(D)DJ using only V delta 2 and V delta 3 was recognized in two patients. We found no V2D delta 3, V3D delta 3, or V1(D)DJ delta rearrangement patterns. Five of nine cases with DDJ delta were positive for cytoplasmic CD3 epsilon(CyCD3 epsilon). Our data suggest that DDJ delta joining occurs at an early stage during T cell differentiation, followed by rearrangements of V delta to the DDJ delta complex. Furthermore, our findings suggest that DDJ delta recombination occurs earlier than expression of CyCD3 epsilon protein products. DDJ delta rearrangements have never been observed in non-T cell malignancies, such as precursor-B-ALL or acute myeloid leukemia. Therefore, detection of DDJ delta rearrangement in the TcR-delta locus is a useful tool to establish lineage and clonality of leukemic cells in the most immature stages of T cell development.
 ...
PMID:High prevalence of T cell receptor D delta 2(D delta)J delta rearrangement in CD7-positive early T cell acute lymphoblastic leukemia. 861 42

The growth of cells in vitro and in vivo is regulated by several environmental signals among which growth factors (cytokines) figure prominently. FLT3 is a novel cytokine receptor with intrinsic ligand-stimulated (FLT3 ligand, FL) tyrosine kinase activity. Here, using a specific anti-FLT3 monoclonal antibody (McAb) and flow cytometry we determined the expression pattern of the receptor protein in 55 human leukemia-lymphoma cell lines and in 20 primary samples from patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). FLT3 receptor surface expression was found predominantly in pre-B cell, myeloid and monocytic cell lines and in pre-B-ALL and AML cells, FL was overexpressed in baby hamster kidney cells producing a recombinant protein that was functional in receptor binding and signaling. Incubation with FL induced 3H-thymidine uptake-measured proliferation in some myeloid cell lines and in 2/9 AML cases. The strongest proliferative response was seen in the two growth factor-dependent myeloid leukemia cell lines MUTZ-2 and OCI-AML-5. Long-term substitution of the commonly used cytokines with FL sustained the continuous proliferation of these two cell lines suggesting that also upon permanent activation FLT2 can function as a mitogenic signaling molecule. Despite the high density of FLT3 receptor expression on cultured and fresh pre-B-ALL cells, no proliferation could be stimulated in any of these specimens. Incubation with the anti-FLT3 McAb had agonistic proliferative effects in MUTZ-2 and OCI-AML-5; and anti-FL reagent blocked FL-stimulated proliferation. To summarize, we demonstrated that FL is effective in inducing proliferation of leukemic myeloid cells and that protein expression does not necessarily indicate an FL-responsive cell. While the present data clearly demonstrate that FL might play a proliferative role in leukemogenesis, further studies are needed to clarify whether the signals provided by FL:FLT3 interaction are confined to a proliferation-inducing function or whether maturational progression could also be elicited in certain cells.
 ...
PMID:Effects of FLT3 ligand on human leukemia cells. I. Proliferative response of myeloid leukemia cells. 863 35

A ligand for the flt3 tyrosine kinase receptor (flt3R) has recently been cloned. Forty-three cases of childhood acute myeloid leukemia (AML) and 27 cases of childhood acute lymphocytic leukemia (ALL) were examined by flow cytometric analysis for cell-surface flt3R and proliferative response in vitro to flt3 ligand (flt3L). Flt3R was commonly expressed on the cell surface of leukemic cells from all AML subclasses and B-ALL, but we did not detect cell-surface flt3R on T-ALL. Flt3L alone induced the proliferation of the monocytic AML-M5 cells and some erythroleukemic AML-M6 cells. Some isolated instances of weak proliferative responses were also noted in other AML subclasses. Interleukin-4 (IL-4) alone inhibited the proliferation of a group of AML-M5 cells and, when combined with flt3L, suppressed the proliferative effect of flt3L. In general, B-ALL and T-ALL cells failed to respond to flt3L alone or in the presence of combinations of IL-2, IL-3, or IL-7.
 ...
PMID:Effects of flt3 ligand on acute myeloid and lymphocytic leukemic blast cells from children. 864 69

Using 7-amino-actinomycin-D/pyronin Y (7AAD/PY), we analyzed the surface phenotypes and cell cycle of 22 hematopoietic cell lines based on their cellular DNA/RNA content. Populations of G1a, G1b, S, and G2M, the DNA index (DI), and the RNA index of S phase (SRI) were calculated by means of DNA/RNA dot plots. Two new parameters were extracted from the cell-cycle profiles: the nucleic acid index of S phase (NI) and the coefficient of variations in the RNA at S phase (SVC). DNA/RNA dot plots of cell lines revealed four characteristic profiles of the cell cycle, defined with the calculated NI and SCV. These were type 0 (small NI, large SCV), type I (small NI, small SCV), type II (large NI, small SCV), and type III (large NI, large SCV). Type O included four stem cell lines: one t(1;19) leukemia, two Ph1+ acute lymphocytic leukemia (ALL), and one biphenotypic crisis of chronic granulocytic leukemia (CGL). Type I included five ALL cell lines: three T-ALL and two common B-ALL. Type II contained 10 myeloid cell lines: five AML and five myeloid crisis of CGL. Type III contained three relatively immature lymphoma cell lines: two Burkitt's lymphoma and one follicular center lymphoma. Calculated NI/SCV (%) were as follows: type 0, 2.27 +/- 0.19/16.7 +/- 3.7; type I, 2.20 +/- 0.30/11.1 +/- 0.7; type II, 3.64 +/- 0.52/11.8 +/- 1.0; and type III, 3.60 +/- 0.53/17.5 +/- 1.9. Cell-cycle analysis of blasts using 7AAD/PY combined with surface phenotyping may yield important information for classifying hematopoietic malignancy within 2 hours of patient admission.
 ...
PMID:Profile of cell cycle in hematopoietic malignancy by DNA/RNA quantitation using 7AAD/PY. 869 48

In 1996 progress has been made toward a better understanding of acute leukemias, their biology, the effects of different intensity or subtype-specific chemotherapy, and the contribution of bone marrow transplantation. In acute lymphoblastic leukemia, high-dose cytarabine in induction and in postremission treatment improves the cure rate, whereas dose reduction of daunorubicin in older patients worsens response and increases mortality. After acute promyelocytic leukemia has been successfully treated by retinoids, another subtype-specific chemotherapy containing high-dose methotrexate has overcome the primarily poor prognosis of B-cell acute lymphoblastic leukemia. The leukemic stem cell of acute myeloid leukemia representing minimal residual disease, producing disease progression in the patients, and initiating long-term growth in cultures or immunodeficient mice appears as a primitive multipotent cell. Leukemic transformation is reflected either by the specific balanced chromosome translocations or by chromosome deletions or losses. They are associated with histories of cytotoxic drugs such as epipodophylotoxins and anthracyclines or alkylating agents. Alternatively, both kinds of aberrations develop spontaneously with ethnic differences in special subtypes. Cytogenetics also determine favorable and unfavorable prognosis both for chemotherapy and bone marrow transplantation. In acute lymphoblastic leukemia high-risk and nonstandard-risk patients seem to benefit from allogeneic transplantation, whereas in acute myeloid leukemia there is no adequate basis for risk-adapted stratification between treatment modalities. New prospects lie in a more successful use of the effects of treatment intensification possibly supported by autologous blood stem cell transplantation. On the basis of standardized treatment, future clinical research can address the role of biologic features of the individual leukemia such as specific chromosome aberrations, fusion genes, expression of oncogenes, and monitoring of minimal residual disease.
 ...
PMID:Treatment of adult acute leukemia. 909 Apr 90

The cDNAs encoding wild type (WT) human receptor tyrosine kinase c-Kit and a constitutively activated mutant, V816Kit, were introduced into granulocyte-macrophage colony-stimulating factor (GM-CSF )-dependent early murine hemopoietic cells, which had been transformed with activated Myb. WTKit cells were able to grow in the presence of the human ligand for Kit, stem cell factor (SCF ), but displayed reduced growth and clonogenic potential in either SCF or GM-CSF compared with the parental cells in GM-CSF. In contrast, V816Kit cells grew without factor at a higher rate than the parental cells in GM-CSF and displayed increased clonogenicity. Dissection of the growth characteristics in liquid culture showed that in the presence of appropriate factors, the different populations had similar proliferation rates, but that V816Kit profoundly increased cell survival compared with WTKit or parental cells. This suggests that the signals transduced by WTKit activated with SCF, and by V816Kit, were not identical. Also, WTKit and V816Kit-expressing cells both varied from the early myeloid progenitor phenotype of the parental cells and gave rise to a small number of large to giant adherent cells that expressed macrophage (alpha-naphthyl acetate) esterase and neutrophil (naphtol-AS-D-chloroacetate) esterase, were highly phagocytic and phenotypically resembled histiocytes. Thus, WTKit activated by SCF and V816Kit were able to induce differentiation in a proportion of Myb-transformed myeloid cells. The factor independent V816Kit cells, unlike the parental and WTKit expressing cells, were shown to produce tumors of highly mitotic, invasive cells at various stages of differentiation in syngeneic mice. These results imply that constitutively activated Kit can promote the development of differentiated myeloid tumors and that its oncogenic effects are not restricted to lineages (mast cell and B-cell acute lymphoblastic leukemia), which have been reported previously. Furthermore, the mixed populations of cells in culture and in the tumors phenotypically resembled the leukemic cells from patients with monocytic leukemia with histiocytic differentiation (acute myeloid leukemia-M5c), a newly proposed subtype of myeloid leukemia.
 ...
PMID:Expression of constitutively activated human c-Kit in Myb transformed early myeloid cells leads to factor independence, histiocytic differentiation, and tumorigenicity. 937 65


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>