Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To explore the difference of biological characteristics between two subpopulations of adult bone marrow mesenchymal stem cells (MSC), this study was designed to observe the morphological feature and immunophenotype of the adult MSC in the ex vivo culture, the mononuclear cells isolated from normal adult bone marrow were cultured in DMEM with 10% fetal bovine serum. Cell morphology, immunophenotype and cell cycle of two different subgroups were investigated. Cells from 80% confluence were passed through a 10 microm filter, then the fillered cells were cultured in the semisolid methylcellulose medium. The results showed that (1) two different subpopulations were observed in the ex vivo culture. The fibro-like cell was called mature MSC (mMSC) and the smaller round cell was defined rapidly as MSC self-renewing cells (RS cells); (2) the average proportion of cells in G(0)/G(1) of RS cells was approximately 99%, but that of mMSCs was 90%; (3) both of the two populations were negative on the lineage-committed antigen (such as CD34, CD45, CD3, CD19, CD33, HLA-DR, CD38), while positive on the expression of CD90, CD105, C166, CD29, CD44, CD49e, CD54, CD13. However, the expression of these antigens on RS cells was weaker than that on mMSC, but CD117 and KDR were higher expressed when compared with the mMSC; (4) after 4 to 5 week semisolid culture, no hematopoietic progenitor cell colonies were observed. It is concluded that adult MSCs are heterogeneous in that distinct morphological populations exist. The RS cells appear to be the more primitive with greater potential for self-renewal and multilineage differentiation.
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PMID:[Comparative study on various subpopulations in mesenchymal stem cells of adult bone marrow]. 1574 36

The case of a patient presenting with a myeloproliferative disorder (MPD) characterized by a t(8;22) (p12;q11) translocation was investigated. The rearrangement resulted in the production of BCR-FGFR1 and FGFR1-BCR chimeric transcripts after in-frame fusions of BCR exon 4 with FGFR1 exon 9 and FGFR1 exon 8 with BCR exon 5, respectively. The four previously reported patients with such translocation presented with an atypical chronic myeloid leukemia (CML) without Philadelphia chromosome. In addition to a myeloproliferation, the patient had a B cell proliferation. The phenotypic characterization of the lymphoid cells in the bone marrow showed a continuum of maturation from blast B cells to polyclonal lymphocytes. In the blood, B cells showed a complete polyclonal maturation. The BCR-FGFR1 gene fusion was detected by dual-color fluorescence in situ hybridization in both CD19- and CD19+ populations. In contrast to the other FGFR1-MPDs that show myeloid and T cell proliferation, we propose that this t(8;22) MPD is a myeloid and B cell disease, and potentially a novel type of hematological disease. Although the FGFR1-MPD is rare, its study provides interesting clues to the understanding of hematopoietic stem cell biology and oncogene activation.
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PMID:Dual lympho-myeloproliferative disorder in a patient with t(8;22) with BCR-FGFR1 gene fusion. 1587 Aug 60

We have recently described a CD19(-) B220(+)CD117(low) bone marrow subpopulation with B, T, and myeloid developmental potential, which we have called "early progenitors with lymphoid and myeloid potential" or EPLM. These cells also expressed Fms-like tyrosine kinase 3, Flt3, or CD135. Treatment of mice with the corresponding ligand, Flt3L, showed a 50-fold increase in EPLM. In addition to the expected increase in dendritic cell numbers, Flt3L treatment had a reversible inhibitory effect on B lymphopoiesis. Limiting dilution analysis of sorted EPLM from Flt3L-treated mice showed that B-lymphocyte progenitor activity was reduced 20-fold, but that myeloid and T-cell progenitor activity was largely preserved. EPLM from treated mice transiently reconstituted the thymus and bone marrow of recipient mice, generating cohorts of functional T and B cells in peripheral lymphoid organs. Thus, Flt3L treatment results in a dramatic increase in a novel bone marrow cell with lymphoid and myeloid progenitor activity.
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PMID:Increasing Flt3L availability alters composition of a novel bone marrow lymphoid progenitor compartment. 1667 11

We established a leukemia cell line derived from therapy-related acute myeloid leukemia with the t(11;19) by xenotransplantation into the NOD/SCID mouse with IL-2Rgamma(c)-/- (NOG mouse). The cell line, TRL-01, could be serially transplanted from mouse to mouse and also grown in an adherence-dependent manner on a murine bone marrow stroma cell line, HESS-5. TRL-01 had the same immunophenotype as the original leukemia cells: positive for CD13, CD33, CD11a, CD18, CD29, CD49d, CD49e, CD54, CD62L, and CD117, and negative for CD3, CD4, CD8, CD19, CD34, CD41a, CD41b, CD135, and myeloperoxidase. Translocation (11;19)(q23;p13) in both the original sample and TRL-01 generated MLL-ENL chimeric transcripts joining exon 6 and exon 4, respectively, which has a novel isoform. In cultures of TRL-01, addition of GM-CSF, SCF, and G-CSF and adhesion to fibronectin-coated plates promoted transient proliferation and survival, although they did not support long-term culture. Subcutaneous injection caused a tumor to form only when HESS-5 was coinjected at the same site. These results suggest that TRL-01 is a useful cell line for studying not only the leukemia-related biology of MLL-ENL but also the intercellular association between leukemia and stroma.
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PMID:Establishment of a myeloid leukemia cell line, TRL-01, with MLL-ENL fusion gene. 1687 30

A combination of chromosomal translocations associated with bcl-2 re-arrangement (t(14;18)) and c-myc re-arrangement (t(8;14), t(8;22), or t(2;8)) is a rare event. We describe the first cell line exhibiting t(14;18) and t(8;22), which will enable us to study the interactions of bcl-2 and c-myc systematically. Cell culture was started with circulating lymphoma cells from the peripheral blood of an adult male Caucasian patient with Burkitt's lymphoma after the second relapse. The cells grew spontaneously without cytokines, fulfilled all criteria of a cell line and were analysed. An Epstein-Barr virus (EBV) genome-negative cell line (DoGKiT) has been established. RC-banding analysis of the chromosomes showed a complex karyotype with a modal number of 48, XY, dup(1)(q31;q44), t(8;22)(q24;q11), der(10), t(14;18)(q32;q21), add(16)(pter), dup(17)(q12q24), +der(18), +20. The combination of t(8;22)(q24;q11), a variant translocation of Burkitt's lymphoma and t(14;18)(q32;q21), typical for follicular lymphoma (FL), was confirmed by FISH and SKY-analysis. Surface marker studies of the cell line showed that the cells were positive for CALLA (CD10), CD19, cyCD22, cyCD79a and HLA-DR and negative for TdT, IgM, CD5 and CD23. To our knowledge, this is the first established cell line carrying these two translocations. In contrast to already established cell lines carrying the more common combination of t(8;14)(q24;q32) and t(14;18)(q32;q21) with both IgH alleles being involved in translocations, the cell line DoGKiT carries only one translocated IgH allele. This cell line may serve as an important tool in the study of the combination of the chromosomal translocations t(14;18) and t(8;22) and in molecular genetic studies of transformed FL.
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PMID:A human Burkitt's lymphoma cell line carrying t(8;22) and t(14;18) translocations. 1762 30

Translocation (8; 21)/AML1-ETO is considered a favorable cytogenetic abnormality in acute myeloid leukemia (AML). However, associated KIT activating mutations confer poor outcome. The immunophenotype associated with KIT mutations in AML1-ETO has not previously been elucidated. We retrospectively reviewed the immunophenotype by flow cytometry of 56 cases of AML with t(8; 21) and compared them with 100 cases of AML without t(8; 21). In 21 t(8; 21) cases, we sought KIT mutations by direct sequencing. Although CD19 and CD56 were aberrantly expressed in 42 (75%) of 56 and 46 (82%) of 56 cases, respectively, with t(8; 21), these markers were only expressed in 4% and 25%, respectively, without t(8; 21) (P < .001). However, the 5 KIT-mutated cases (D816H, 3; D816Y, 1; and N822K, 1) of t(8; 21) AML had diminished CD19 expression (P = .04) with definite CD56 expression (P = .30) on myeloid blasts. Our study suggests that KIT activating mutations in AML with t(8; 21) are associated with diminished CD 19 and positive CD56 expression on leukemic blasts and, thus, can be phenotypically distinguished from AML1-ETO leukemias without KIT mutations.
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PMID:Immunophenotypic profile predictive of KIT activating mutations in AML1-ETO leukemia. 1787 4

PAX5 is a transcription factor essential for B-cell development. Recently, it has been found as a frequent target of aberrancies in childhood acute lymphoblastic leukemia (ALL; 30% of B cell ALL cases), showing monoallelic loss, point mutations, or chromosomal translocations. The role of these aberrancies is still poorly understood. We previously cloned the PAX5/TEL fusion gene in a patient affected by B-cell precursor ALL with a t(9;12) translocation. This is the first report investigating the molecular and functional roles of PAX5/TEL protein in vitro from murine wild-type pre-BI cells. We showed that PAX5/TEL protein acts as an aberrant transcription factor with repressor function, recruiting mSin3A, down-regulating B220, CD19, BLNK, MB-1, FLT3, and mu heavy chain expression, thus suggesting a block on B-cell differentiation. In a PAX5-deficient context, the presence of PAX5/TEL did not replace PAX5 functions. PAX5/TEL protein enhances cell migration towards CXCL12, with the overexpression of CXCR4. Moreover, the presence of the fusion gene overcomes interleukin-7 withdrawal and interferes with transforming growth factor-beta1 pathway, inducing resistance and conferring cells an advantage in proliferation and survival. Thus, in vitro, the PAX5/TEL protein has a dominant effect on wild-type PAX5, interferes with the process of B-cell differentiation and migration, and induces resistance to apoptosis. Taken together, these phenomena likely represent key events in the process of B-cell transformation.
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PMID:PAX5/TEL acts as a transcriptional repressor causing down-modulation of CD19, enhances migration to CXCL12, and confers survival advantage in pre-BI cells. 1817 10

Commitment of hematopoietic progenitor cells to B-lymphoid cell fate has been suggested to coincide with the development of PAX5-expressing B220(+)CD19(+) pro-B cells. We have used a transgenic reporter mouse, expressing human CD25 under the control of the B-lineage-restricted Igll1 (lambda5) promoter to investigate the lineage potential of early progenitor cells in the bone marrow. This strategy allowed us to identify a reporter expressing LIN(-)B220(-)CD19(-)CD127(+)FLT3(+)SCA1(low)KIT(low) population that displays a lack of myeloid and a 90% reduction in in vitro T-cell potential compared with its reporter-negative counterpart. Gene expression analysis demonstrated that these lineage-restricted cells express B-lineage-associated genes to levels comparable with that observed in pro-B cells. These data suggest that B-lineage commitment can occur before the expression of B220 and CD19.
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PMID:B-lineage commitment prior to surface expression of B220 and CD19 on hematopoietic progenitor cells. 1849 58

Acute myeloid leukemia with t(8;21)(q22;q22) is a distinct type of leukemia considered to have a favorable prognosis. However, some patients rapidly succumb to disease despite chemotherapy. We studied 56 patients with acute myeloid leukemia associated with t(8;21) and correlated clinicopathologic, cytogenetic and molecular findings with outcome to identify markers of prognosis. In a subset of patients, we also assessed the status of the c-KIT, FLT3 and RAS genes. There were 31 men and 25 women, with a median age of 38 years (range 4-76). The follow-up period ranged from 17 to 104 months (median 52). At the last follow-up, 29 patients had died, 25 patients were in complete remission and two patients were alive with disease. The median survial was 38 months. The 5-year overall survival rate of newly diagnosed patients was 56%. Most patients (39/56, 70%) had chromosomal aberrations in addition to t(8;21), with loss of a sex chromosome (39%) being most common followed by del(9q)(q21-22) (11%) and trisomy 8 (7%). These aberrations, however, did not predict survival. C-KIT (D816V or D816Y), FLT3 (ITD or D835) and RAS mutations were detected in 26, 10 and 7%, respectively, of cases assessed. The 5-year overall survival rate of patients with mutated leukemia was 20%. No mutations were observed in three patients who died within 7 months of diagnosis. Leukocytosis or CD56 expression did not correlate with a poor survival nor did the levels of CD19 expression predict c-KIT mutation status. We conclude that acute myeloid leukemia associated with t(8;21) is a heterogeneous disease with poor survival in a subset of patients unrelated to common secondary cytogenetic aberrations.
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PMID:Acute myeloid leukemia harboring t(8;21)(q22;q22): a heterogeneous disease with poor outcome in a subset of patients unrelated to secondary cytogenetic aberrations. 1853 54

Gene profiling studies of patients with chronic lymphocytic leukemia (CLL) has revealed increased expression of Ror1, a cell surface receptor tyrosine kinase. The aim of present study was to analyze gene and protein expression of Ror1 in CLL cells and normal blood leukocytes. Gene expression analysis reverse transcription-polymerase chain reaction of ROR1 revealed that all patients with CLL (n = 100) spontaneously expressed ROR1 mRNA whereas enriched blood B and T cells as well as granulocytes from healthy donors (n = 10) were negative. A strong nonphysiological activation signal (PMA/ionomycin) was required to induce expression in vitro in normal lymphocytes. Major genomic aberrations (mutations or truncation) of ROR1 were not observed. Protein expression was analyzed by Western blot using a panel of polyclonal anti-Ror antibodies as well as flow cytometry. Blood lymphocytes from 18/18 CLL patients, but none of the 10 healthy donors, expressed surface Ror1. The majority of CLL cells exhibited Ror1 surface expression (71% mean; range 36-92%) with a mean fluorescence intensity (MFI) of 20 (range 10-45). The corresponding MFI of CD19 on CLL cells was 26 (range 9-48). There was no difference in the Ror1 protein expression comparing IgVH mutated and unmutated cases as well as progressive and nonprogressive CLL patients. Two different variants of the Ror1 protein, 105 and 130 kDa, were identified. The Ror1 protein expression in patients with CLL but not in normal leukocytes merits further studies of its role in the pathobiology of CLL, which may provide a basis for development of Ror1 directed targeted therapy.
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PMID:Ror1, a cell surface receptor tyrosine kinase is expressed in chronic lymphocytic leukemia and may serve as a putative target for therapy. 1854 92


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