Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Bcl-2 proto-oncogene was discovered at the t(14;18) breakpoint found in most follicular B-cell lymphomas and some diffuse large-cell lymphomas. Bcl-2 is unique among proto-oncogenes, being localized to mitochondria and extending cell survival by blocking programmed cell death. We examined Bcl-2 protein expression in 82 hematologic malignancies and reactive lymphoid processes. All lymphomas with Bcl-2 rearrangement demonstrated high levels of Bcl-2 protein. However, most follicular and diffuse lymphomas without Bcl-2 rearrangement also displayed intense Bcl-2 staining. In these cases, mechanisms other than classic translocation may be deregulation Bcl-2. The pattern of Bcl-2 staining in follicular lymphoma is the inverse of the pattern in reactive hyperplasia, confirming a role for Bcl-2 immunolocalization in routine diagnosis. Small lymphocytic malignancies, including small lymphocytic lymphoma, mantle zone lymphoma, and chronic lymphocytic leukemia, expressed intermediate levels of Bcl-2. Bcl-2 protein varied in plasma cell dyscrasias. Bcl-2 protein levels in T-cell lymphomas reflected their corresponding stage of development. No substantial Bcl-2 was present in the Reed-Sternberg cells of nodular sclerosing Hodgkin's disease. Chronic myelogenous leukemia was strongly positive for Bcl-2, consistent with the presence of Bcl-2 in normal myeloid progenitors. Immunohistochemistry identified an expanded spectrum of hematopoietic neoplasms in which Bcl-2 may provide a cell survival advantage.
 ...
PMID:Immunolocalization of the Bcl-2 protein within hematopoietic neoplasms. 186 40

The v-abl gene in Abelson virus induces pre-B-cell lymphoma in mice while the BCR/ABL oncogene is associated with chronic myelogenous leukemia and some cases of acute lymphocytic leukemia in humans. Understanding the mechanisms by which these oncogenes affect various cell types has been hampered by a paucity of experimental systems that reproduce the range of biological effects associated with them. We have developed an experimental system in which murine hematopoietic stem cell populations are infected with either v-abl or BCR/ABL retroviruses and are used to reconstitute lethally irradiated mice. Irrespective of the form of activated abl, greater than 90% of the animals reconstituted with such cells develop tumors. About 50% of them develop a myeloproliferative syndrome that shares several features with the chronic phase of chronic myelogenous leukemia; the remaining animals succumb to pre-B-cell lymphomas. The myeloproliferative syndrome is characterized by large numbers of clonally derived, infected myeloid cells. This model will allow study of the mechanism by which activated abl genes affect hematopoietic precursors in chronic myelogenous leukemia. Furthermore, our results demonstrate that introduction of an activated abl gene into the appropriate target cell, not the structure of the gene, is the major determinant in myeloid cell specificity.
 ...
PMID:Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. 220 61

An antiserum specific to esterase Ib was produced in a rabbit. The antigen-antibody reaction was visualized by the strong esterase activity in the precipitin band in Ouchterlony double diffusion and immunoelectrophoresis. Immunohistochemical procedure demonstrated strong staining in the monocyte-infiltrated splenic sections and tissue sections of true histiocytic lymphoma. Negative results were observed in T- and B-cell lymphomas, granulocytic sarcoma, and chronic granulocytic leukemia. This antibody may be useful for the identification of monocytes and histocytes in paraffin-embedded tissue sections.
 ...
PMID:Immunohistochemical detection of monocytes by the antiserum specific to monocytic esterase. 388 78

Previous studies have demonstrated that the common acute lymphoblastic leukemia antigen (CALLA) is expressed by leukemic cells from approximately 80% of patients with non-T-cell ALL and 30%-50% of patients with chronic myelocytic leukemia in blast crisis. A small number of normal bone marrow and fetal liver cells also express CALLA, but the functional role of this molecule is unknown. In the present study, we have used a monoclonal antibody (J5) specific for CALLA to study the expression of this antigen in non-Hodgkin's lymphomas. Within the B-cell lymphomas, it was found the CALLA was expressed by almost all Burkitt's and nodular poorly differentiated lymphocytic lymphomas. Within the T-cell lymphomas, CALLA was expressed in 40% of patients with lymphoblastic lymphoma. Three of 3 Burkitt's lymphoma cell lines and three of eight T-lymphoblast cell lines were also found to express CALLA. Normal spleen, lymph node, and thymus cells were not reactive with J5 antibody. These findings indicate that expression of CALLA is not limited to relatively undifferentiated leukemic lymphoblasts but also occurs in more differentiated lymphoid malignancies. However, normal differentiated lymphoid cells in lymph node, spleen, and thymus, which have a phenotype similar to that of lymphoma cells, do not appear to express CALLA.
 ...
PMID:Expression of common acute lymphoblastic leukemia antigen (CALLA) by lymphomas of B-cell and T-cell lineage. 697 48

Systemic mast cell disease is characterized by an abnormal infiltration of mast cells involving several parenchymal organs and the bone marrow. Its spectrum of clinical and histologic presentation is highly variable and is not necessarily correlated with prognosis. Mast cell disorders presenting as atypical infiltrates in the bone marrow may simulate or be associated with other hematolymphoid malignancies, from which they must be distinguished. The paucity of reliable histochemical and immunohistochemical markers for the detection of mast cells in paraffin sections further confounds this diagnosis. The authors have employed immunohistochemistry for the C-KIT encoded tyrosine kinase receptor protein, CD117, for detection of mast cells on paraffin sections of 89 bone marrow specimens including systemic mast cell disease and other disorders. CD117 staining was found in all cases of mast cell disorders (seven of seven), and in one case of chronic myelogenous leukemia in blast crisis. None of the other myeloid disorders tested (0 of 16), or any of the cases of Hodgkin's disease (0 of 12), B-cell lymphomas (0 of 32), T-cell lymphomas (0 of 3), or histiocytic proliferations (0 of 3) showed staining for CD117. CD117 expression is effective in the separation of mast cell disease from disorders that may simulate it histologically.
 ...
PMID:Utility of paraffin section immunohistochemistry for C-KIT (CD117) in the differential diagnosis of systemic mast cell disease involving the bone marrow. 1063 91

Until the end of the 19th century the possibility that a tumor could be rejected merely by the body's immune defense was no more than a vision. After more than 100 years of preclinical and clinical research in the field, the vision of cancer immunotherapy became real and has, with multiple tools, successfully entered clinical standard practice. Non-specific mediators of immune defense, such as BCG for treatment of superficial bladder cancer or interferon-alpha for treatment of chronic myelogenous leukemia and hairy cell leukemia, can induce durable remissions. In particular, antigen-specific mediators of immune defense represent promising agents for targeted cancer therapies. Antibody-based treatment of B-cell lymphomas and breast cancer has dramatically improved disease response without major toxicity. A large number of new antibodies targeting different epitopes on a variety of malignant cells are now approaching clinical approval. Allogeneic stem cell transplantation for treatment of leukemia and certain cancers represents the first T cell-based adoptive immunotherapy with large-scale clinical application. Experimental T cell-based immunotherapies with promising clinical perspectives include tumor vaccines, adoptive transfer of autologous tumor-specific effector cells and the genetic transfer of tumor-specific T cell receptors into the patient's lymphocytes. These facts demonstrate that immunotherapy has now been established as the fourth column of cancer therapy besides surgery, radiotherapy, and chemotherapy. On the basis of its already proven efficacy, the usually favorable toxicity profiles and the development perspectives of the experimental approaches a further and more rapid expansion can be expected.
 ...
PMID:Immunotherapy of cancer: from vision to standard clinical practice. 1506 41

ICSBP (interferon consensus sequence binding protein)/IRF8 (interferon regulatory factor 8) is an interferon gamma-inducible transcription factor expressed predominantly in hematopoietic cells, and down-regulation of this factor has been observed in chronic myelogenous leukemia and acute myeloid leukemia in man. By screening about 1200 murine leukemia virus (MLV)-induced lymphomas, we found proviral insertions at the Icsbp locus in 14 tumors, 13 of which were mature B-cell lymphomas or plasmacytomas. Only one was a T-cell lymphoma, although such tumors constituted about half of the samples screened. This indicates that the Icsbp locus can play a specific role in the development of mature B-lineage malignancies. Two proviral insertions in the last Icsbp exon were found to act by a poly(A)-insertion mechanism. The remaining insertions were found within or outside Icsbp. Since our results showed expression of Icsbp RNA and protein in all end-stage tumor samples, a simple tumor suppressor function of ICSBP is not likely. Interestingly, proviral insertions at Icsbp have not been reported from previous extensive screenings of mature B-cell lymphomas induced by endogenous MLVs. We propose that ICSBP might be involved in an early modulation of an immune response to exogenous MLVs that might also play a role in proliferation of the mature B-cell lymphomas.
 ...
PMID:The Icsbp locus is a common proviral insertion site in mature B-cell lymphomas/plasmacytomas induced by exogenous murine leukemia virus. 1678 Sep 17

A better understanding of the biology and pathogenesis of hematological malignancies has led to the development of immunotherapeutic and immunoregulatory drugs. Many of these agents have revolutionized the current treatment modalities, while others are under investigation. Rituximab (anti-CD20 antibody) has been established as the gold standard of treatment for aggressive B-cell lymphomas in combination with CHOP and has shown significant activity as monotherapy in the treatment of indolent B-cell lymphomas. In follicular lymphomas the combination of Rituximab with chemotherapy improves the outcome compared to chemotherapy alone. CD 20-based radioimmunotherapy, with the advantage of the bystander effect, represents an additional therapeutic alternative in B-cell lymphomas and may produce tumor regression in Rituximab resistant patients. The anti-CD52 monoclonal antibody, alemtuzumab, further expands the armamentarium against lymphoid malignancies producing high response rates in these entities. Antibody-targeted chemotherapy such as gemtuzumab ozogamicin, consisting of an anti-CD33 antibody combined to calicheamicin, has shown efficacy in the treatment of refractory acute myeloid leukemia; exact indications, timing and dosing schedule for optimized efficacy remain to be determined. Interferons have proven significant activity in cutaneous lymphomas, hairy cell leukemia and chronic myelogenous leukemia by mechanisms that are not fully elucidated. Thalidomide, by acting as an immunomodulatory and antiangiogenic agent can modulate neoplastic cells microenvironment and lead to disease control in multiple myeloma as well as in numerous other hematological malignancies. Bortezomib, a proteasome inhibitor, displays significant anti-tumor activity, especially in multiple myeloma and lymphoproliferative disorders. The addition of these agents in therapeutic regimens has improved considerably the treatment of hematological malignancies.
 ...
PMID:Immunotherapeutic and immunoregulatory drugs in haematologic malignancies. 1701 50

Aberrant micro RNA (miRNA) expression has been described in human malignancies including B-cell lymphomas. We here report BCR-ABL- and c-MYC-dependent regulation of miRNA expression in chronic myeloid leukemia (CML) using microarray analysis (miCHIP) and miRNA-specific quantitative real-time reverse transcriptase-polymerase chain reaction (miR-qRT-PCR). In 3 bcr-abl-positive cell lines, expression of miRNAs encoded within the polycistronic miR-17-92 cluster is specifically down-regulated (2- to 5-fold) by both imatinib treatment and anti-BCR-ABL RNA interference (RNAi). In addition, anti-c-MYC RNAi reduces miR-17-92 expression in K562 cells in which miRNAs can specifically repress reporter gene expression, as demonstrated by specific miRNA inhibition with antagomirs. Furthermore, lentivirus-mediated overexpression of polycistronic miRNAs in K562 cells confers increased proliferation, partial resistance against anti-c-MYC RNAi, and enhanced sensitivity to imatinib-induced cell death. Finally, we determined miR-17-92 expression in purified normal (n = 4), early chronic-phase (CP) (n = 24), and blast-crisis (BC) (n = 7) CML CD34(+) cells and found up-regulation of polycistronic pri-miRNA transcripts in CML and mature miRNAs in CP but not in BC CML. These data are in accordance with a BCR-ABL-c-MYC-miR-17-92 pathway that mediates enhanced miRNA expression in CP but not BC CML CD34(+) cells. Altered miRNA expression may contribute to the pathophysiology of the disease and may provide potential targets for therapeutic intervention.
 ...
PMID:Expression of the miR-17-92 polycistron in chronic myeloid leukemia (CML) CD34+ cells. 1728 33

In last two decades newer therapies in cancer treatment have emerged and have opened new horizons. New term of targeted therapy has emerged and for certain malignancies the paradigm has really changed after the introduction of these agents. We have learnt and have seen the outcome of some diseases after the addition of these monoclonal antibodies (MoABs) and tyrosine kinase inhibitors (TKIs). Rituximab a MoAB against CD-20 has really paved its role in the treatment of B-cell lymphomas and become the sort of standard therapy. The TKIs are newer agents available in a pill form and have inhibited many pathways at cellular level which are necessary for cancer development. Imatinib has really changed the prognosis and outcome of chronic myeloid leukemia (CML) remarkably. For those patients who develope intolerance to imatinib or their disease became resistant to the imatinib the newer agents like dasatinib and nilotinib are second line options. The major edge of these newer agents is more potency with low side-effect profile. The major concern remains the cost.
 ...
PMID:Old disease, new targets. Part-II, haematological malignancies. 1975 5


1 2 Next >>