Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transplantation of hematopoietic precursor cells is an established therapy today in the treatment of hematological malignancies. Cells from different sources [bone marrow, peripheral blood, cord blood] and from different donor types [autologous, syngeneic or allogeneic] are used for transplantation. The aim of autologous transplantation is to apply intensive high-dose chemo-radiotherapy and to shorten the duration of aplasia. Allogeneic cells, in addition, are free of potentially contaminating precursor cells and provide a graft-versus-leukemia effect. For all patients, transplantation should be considered at diagnosis as an integral part of treatment strategy and, depending on risk factors, be performed early in the course of disease. Preferred time for patients with high-risk acute leukemias is first complete remission, second complete remission for standard or low-risk acute leukemias. For chronic myeloid leukemia, allogeneic transplantation should be performed within one year of diagnosis, preferably still in first chronic phase. Autologous transplantation can be considered in a protocol setting. For patients with myelodysplastic syndromes of the FAB subtype refractory anemia or refractory anemia with sideroblasts, allogeneic transplantation is the treatment of choice as initial therapy. For patients with refractory anemia and excess of blasts with or without transformation, remission induction should be attempted before transplantation. Autologous transplantation is the preferred treatment strategy for patients with Hodgkin's and non-Hodgkin's lymphoma, for high-risk patients in first complete remission, for other patients in chemotherapy-sensitive first relapse. For patients with myeloma, transplantation should be considered after first line therapy. Age is the main individual patient's risk factor, transplant-related mortality immediately increases in parallel to increasing age. Autologous transplants are limited to patients below 60 to 65 years, allogeneic HLA-identical sibling transplants to patients below 50 to 55 years, and unrelated transplants to patients below 40 to 45 years. Prerequisites for transplant are availability of a donor, access to a transplant bed, informed consent of patient and donor, as well as financial guarantee. Indications for the different hematological malignancies and the major risk factors are discussed.
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PMID:[Indications for bone marrow and peripheral stem cell transplantation in malignant hematological diseases]. 862 66

The survival, proliferation, differentiation and function of normal hematopoietic cells are negatively and positively controlled by various cytokines. Survival and proliferation of leukemic cells appears to be influenced, at least in vitro, by several cytokines. Among the different hematopoietic cell lineages, megakaryocytopoiesis represents a complex and unique hematopoietic system that is thought to be supported by some well-known cytokines; however, the hypothetical lineage-specific main regulator of platelet production, termed thrombopoietin (TPO) had remained elusive. Recently, characterization of the proto-oncogene c-mpl revealed structural homology with the hematopoietic cytokine receptor superfamily, specific expression on cells of the megakaryocytic lineage and functional involvement in megakaryocytopoiesis. Several groups purified and cloned the MPL ligand. Extensive in vitro and in vivo studies have shown that the MPL ligand has activity in stimulating both megakaryocytopoiesis and platelet production proving that this ligand is the long-sought growth factor TPO itself. The MPL receptor was found at the mRNA and/or protein level in 40-80% of primary acute myeloid leukemia (AML) cases in various series. MPL expression was not limited to certain morphological FAB types, although the highest percentages were seen in the M6 (erythroid) and M7 (megakaryocytic) subclasses. Among the myelodysplastic syndromes (MDS), MPL expression was detected in one third of the cases, in particular in refractory anemia with excess of blasts and chronic myelomonocytic leukemia. Lymphoid malignancies such as acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma (NHL) and myeloma were MPL-negative. Among the large panel of human leukemia-lymphoma cell lines studied, MPL expression occurred predominantly in lines with erythro-megakaryocytic phenotypes. Nearly all primary and continuously cultured non-hematopoietic solid tumor samples were negative for MPL expression. A significant portion of AML cases and of erythroid, megakaryocytic and myeloid leukemia cell lines co-expressed TPO and MPL mRNA transcripts, although no biologically active TPO appeared to be secreted by these cells. In several studies TPO induced in vitro proliferation of 14-37% of primary AML cases, predominantly of the M2 and M7 subtypes. TPO significantly enhanced the cytokine-induced growth of AML cells in a substantial fraction of cases responsive to GM-CSF, IL-3, IL-6 or SCF. While none of 30 growth factor-independent erythro-megakaryocytic leukemia cell lines responded to TPO with increased proliferation, TPO strongly augmented the growth of several constitutively cytokine-dependent cell lines (eg HU-3, M-07e, TF-1) which can be made TPO-dependent and used as bioassays. Neither in primary cells nor in cell lines did TPO appear to induce any signs of morphological, functional or immunological differentiation. Expression of the MPL receptor is not correlated with a proliferative response to TPO. In summary, extensive studies on normal human and animal cells demonstrated the specificity and function of the MPL receptor and proved that its ligand TPO is the major physiological regulator of megakaryocytopoiesis. The data reviewed here document the wide expression of the MPL receptor on AML cells and also suggest some proliferative effects on certain leukemia cells, apparently on non-megakaryocytic AML cells as well. Thus, experimental evidence supports the notion that TPO may contribute, at least in part, to leukemogenesis, especially in combination with other hematopoietic cytokines which is of clinical significance. TPO-responsive cell lines represent powerful tools for such analyses.
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PMID:Thrombopoietin: expression of its receptor MPL and proliferative effects on leukemic cells. 875 57

In this study, we examined a large number of patients to clarify the distribution and frequency of a recently described FLT3 tandem duplication among hematopoietic malignancies, including 112 acute myelocytic leukemia (AML), 55 acute lymphoblastic leukemia (ALL), 37 myelodysplastic syndrome (MDS), 20 chronic myelogenous leukemia (CML), 30 non-Hodgkin's lymphoma (NHL), 14 adult T cell leukemia, 15 chronic lymphocytic leukemia (CLL) and 38 multiple myeloma (MM). We also evaluated 71 cell lines derived from 11 AML, 31 ALL, two hairy cell leukemia, three acute unclassified leukemia, 10 CML, 12 NHL including six Burkitt's lymphoma, and two MM. Using genomic PCR of exon 11 coding for the juxtamembrane (JM) domain and first amino acids of the 5'-tyrosine kinase (TK) domain, this length mutation was found only in AML (22/112, 20%) and MDS (1/37). According to the FAB subclassification, they were 5/18 (28%) of M1, 4/29 (14%) of M2, 3/17 (18%) of M3, 6/24 (25%) of M4, 4/20 (20%) of M5 and 1/9 of refractory anemia with excess of blast in transformation. In the various cell lines examined, this abnormality was determined in only one derived from AML and never found in other hematological malignancies. The sequence analysis of the abnormal PCR products revealed that 23 of 24 showed internal tandem duplication with or without insertion of nucleotides. In one AML, insertion and deletion without duplication was determined. All 24 lengthened sequences were in-frame. Duplication takes place in the sequence coding for the JM domain and leaves the TK domain intact. In conclusion, we emphasize that the length mutation of FLT3 at JM/TK-I domains were restricted to AML and MDS. Since all these mutations resulted in in-frame, this abnormality might function for the proliferation of leukemic cells.
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PMID:Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines. 932 77

Treatment-related myelodysplastic syndrome (t-MDS) and acute myelogenous leukemia (t-AML) are now well established as complications of cytotoxic chemotherapy. We experienced a 28-yr-old female patient who developed t-MDS/t-AML with characteristic chromosomal abnormalities including 11q23 chromosomal rearrangement following high-dose chemotherapy with autologous stem cell transplantation (ASCT) for non-Hodgkin's lymphoma. The patient was admitted with bulky abdominal masses of B cell lineage non-Hodgkin's lymphoma. After 2 cycles of systemic chemotherapy of the Vanderbilt regimen, the patient underwent ASCT with high dose chemotherapy of the BEAC regimen. She also received radiation of 48 Gy for the residual periportal lymphadenopathy. The initial cytogenetic analysis of the infused mononuclear cells revealed a normal karyotype. Twenty two months after the ASCT, pancytopenia was noted and her bone marrow aspirate showed dysplastic hemopoiesis with myeloblasts up to 12% of nonerythroid nucleated cells. The patient was diagnosed as t-MDS (refractory anemia with an excess of blasts). Cytogenetic analysis showed complex chromosomal abnormalities including 11q23 rearrangement, which is frequently found in topoisomerase II inhibitor-related hematologic malignancies. Four months later, it was noted that the t-MDS had evolved into an overt t-AML. Cytogenetic analysis showed an evolving pattern with more complex abnormalities. The patient was treated with combination chemotherapy, but her leukemic cells were resistant to the therapy.
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PMID:A case of treatment-related myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemotherapy with autologous stem cell transplantation for non-Hodgkin's lymphoma. 1217 56

Lenalidomide (REVLIMID), an immunomodulatory compound targeting both cancer cells and their microenvironment, has substantial activity in several difficult-to-manage hematological malignancies. In previously treated multiple myeloma, lenalidomide produces high-quality responses combined with sustained disease control. Recently, several randomized studies have demonstrated a clinical benefit of continuous lenalidomide treatment in newly diagnosed multiple myeloma. In many patients with refractory anemia associated with lower risk myelodysplastic syndromes and a 5q chromosome deletion, lenalidomide leads to transfusion independence, considerably improving quality of life. It has a manageable safety profile, and its oral formulation reduces the burden on patients. Several phase III trials are ongoing in other indications currently underserved by conventional therapy, such as chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and prostate cancer. Several early-stage studies are exploring lenalidomide alone and in combination across different hematological malignancies, solid tumors, and immune-related disorders.
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PMID:A review of the history, properties, and use of the immunomodulatory compound lenalidomide. 2143 45