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)

A monoclonal antibody (DU-ALL-1) was generated to common acute lymphoblastic leukemia (cALL) cells by microcytotoxicity and indirect immunofluorescence, DU-ALL-1 reacted only with cALL cell lines and not with the other hematopoietic cell lines tested. Peripheral blood lymphocytes, monocytes, granulocytes and mitogen-activated lymphocytes did not react significantly with this antibody. However, platelets (100%) and normal bone marrow cells (8.5%) reacted with DU-ALL-1. Microcytotoxicity testing of human leukemia cells showed that DU-ALL-1 reacted with cells from a majority of null and pre-B ALL patients (63/77) and with cells from some patients with acute myeloblastic leukemia (4/7) and T-ALL (4/20). DU-ALL-1 was generally non-reactive with cells from patients with B-cell leukemias (2/16) and chronic myelogenous leukemia in blast crisis (0/4). By an indirect immunoperoxidase technique, DU-ALL-1 reacted with a variety of non-hematopoietic tissues, including smooth and cardiac muscle and epithelia from several organs. The DU-ALL-1 antigen had an apparent mol. wt of 24,000 and did not bind to lectins or label with [3H]glucosamine. Thus, DU-ALL-1 defines a 24,000-mol. wt protein which is absent from most peripheral blood mononuclear cells, is expressed on normal platelets and several non-hematopoietic tissues, and may be a useful for subclassifying leukemias.
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PMID:Characterization and distribution of a 24,000-molecular weight antigen defined by a monoclonal antibody (DU-ALL-1) elicited to common acute lymphoblastic leukemia (cALL) cells. 695 29

Many haematologic malignancies carry characteristic chromosomal translocations, which are thought to play an important role in the pathogenesis of these tumours. The t(8; 14) translocation in Burkitt's lymphoma was one of the first characterized at the molecular level. In this translocation the c-myc oncogene at chromosome 8q24 becomes deregulated by enhancer elements of the immunoglobulin heavy chain locus at chromosome 14q32 leading to a very aggressive B cell malignancy. Translocations involving an overexpressed c-myc gene are also found in AIDS-associated lymphoma or in T cell leukaemias, or they develop during tumour progression of a low grade B cell malignancy into a high grade B cell tumour in an additional cytogenetic change. A different mechanism of oncogene activation in a leukaemia specific chromosomal abnormality is found for CML, where c-abl sequences are fused into the bcr locus, or in the t(4; 11) of acute childhood leukaemia involving the recently identified ALL-1 gene at chromosome 11q23 resulting in a malfunctioning, structurally altered oncogene. Thus, in the past molecular and somatic cell genetic studies have clarified many details in aetiology and progression of leukaemias and lymphomas which are useful for applications in clinical diagnostics, and which in the future will be helpful in designing a therapy based on a molecular understanding.
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PMID:Chromosomal translocations in leukaemia. 814 18

Calpain is a calcium-dependent cysteine protease that is implicated in calcium-dependent cell death, and calpain inhibitors are generally considered as inhibitors of apoptosis. To the contrary, in the present study, we found that calpain inhibitor II (CPI-2) triggers rapid apoptosis in acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL) cells. All target cell lines were killed by CPI-2, including: ALL-1, a multidrug-resistant BCR-ABL fusion transcript-positive t(9;22) pro-B ALL cell line; RS4;11, a highly radiation-resistant MLL-AF4 fusion transcript-positive t(4;11) pre-pre B ALL cell line; RAMOS, a highly radiation-resistant and p53-deficient Burkitt's lymphoma cell line; DAUDI, a Burkitt's leukemia/lymphoma cell line; NALM-6, a pre-B ALL cell line; and JURKAT and MOLT-3, two T-lineage ALL/NHL cell lines. CPI-2-induced apoptosis in LYN-deficient and BTK-deficient subclones of the DT-40 lymphoma B cell line as effectively as it did in wild-type DT-40 cells. Thus, CPI-2-induced apoptosis is not dependent on the protein tyrosine kinases LYN or BTK. Notably, caspase inhibitor I effectively inhibited CPI-2-induced apoptosis, suggesting that the inhibition of a CPI-2-susceptible protease results in caspase activation, leading to apoptosis in ALL/NHL cells. Unlike the high calpain-expressing ALL/NHL cell lines, myeloid leukemia cell lines HL-60/AML, K562/CML, and U937/AMML, or solid tumor cell lines BT-20/breast cancer, PC-3/prostate cancer, U373/glioblastoma, and HeLa/epitheloid cancer, were not susceptible to the cytotoxicity of CPI-2. Taken together, our results identify calpain as a new molecular target for the treatment of ALL and NHL. CPI-2 and its analogues represent a promising new class of antileukemia/lymphoma agents that deserves further development.
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PMID:Calpain inhibitor II induces caspase-dependent apoptosis in human acute lymphoblastic leukemia and non-Hodgkin's lymphoma cells as well as some solid tumor cells. 1087 99

A cytogenetic and/or cytochemical study was performed in 166 individuals with leukemia or related disorders, in two major Costa Rican hospitals. In those patients treated at an adult's hospital (14 years old and over), acute leukemias represented 66% of all cases. In that hospital the most frequent types of disorders were, in decreasing order: ANLL (> M1), ALL, CML (all of them showed the Ph chromosome) and MDS. In the cases from a childrens' hospital (< 14 years old) acute leukemias were 98%. Among them the order of frequency was: ALL (70%): ALL-1 (84%), ALL-2 (16%) and ANLL (27%): M5a > M3 > M4 > M5b. In ALL 85% were type B and occurred mostly in women while 15% of them were type T and more frequent in males. There was 5.6% infant leukemia, which presented a similar number of acute lymphoids and myeloids. The cytogenetic pattern was similar among Costa Rica and other tropical and temperate countries.
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PMID:[Cytogenetics and cytochemistry of leukemia patients in 2 neotropical hospitals]. 1135 79