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

The INK4A/ARF locus yields two tumor suppressors, p16INK4A and p14ARF, and is frequently deleted in human tumors. We studied their mRNA expressions in 41 hematopoietic cell lines and in 137 patients with hematological malignancies; we used a quantitative reverse transcription-PCR assay. Normal peripheral bloods, bone marrow and lymph nodes expressed little or undetectable p16INK4A and p14ARF mRNAs, which were readily detected in 12 and 17 of 41 cell lines, respectively. Patients with hematological malignancies frequently lacked p16INK4A expression (60/137) and lost p14ARF expression less frequently (19/137, 13.9%). Almost all patients without p14ARF expression lacked p16INK4A expression, which may correspond to deletions of the INK4A/ARF locus. Undetectable p16INK4A expression with p14ARF expression in 41 patients may correspond to p16INK4A promoter methylation or to normal expression status of the p16INK4A gene. All patients with follicular lymphoma (FL), myeloma or acute myeloid leukemia (AML) expressed p14ARF while nine of 23 patients with diffuse large B cell lymphoma (DLBCL) lost p14ARF expression. Patients with ALL, AML or blast crisis of chronic myelogenous leukemia expressed abundant p16INK4A mRNAs more frequently than patients with other diseases (12/33 vs 6/104, P < 0.01). Patients with FL and high p14ARF expression had a significantly shorter survival time while survival for patients with DLBCL and increased p14ARF expression tended to be longer. These observations indicate that p16INK4A and p14ARF expression is differentially affected among hemato- logical malignancies and that not only inactivation but also increased expression may have clinical significance.
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PMID:Expression of p16INK4A and p14ARF in hematological malignancies. 1055 50

In peripheral blood of at least 50% of healthy individuals, the translocations t(9;22) BCR/ABL, t(14;18) IgH/BCL-2, t(2;5) NPM-ALK and MLL duplications, which characterize chronic myelogenous leukemia and acute lymphoblastic leukemia, follicular lymphoma, anaplastic large cell lymphoma, and acute myelogenous leukemia, respectively, are detectable by sensitive polymerase chain reaction (PCR). No structural differences between these aberrations in normal or disturbed hematopoiesis are apparent. While the total count of t(9;22)- and t(14;18)-positive cells does not exceed 10(4), those with MLL duplications are more frequent and account for approximately 10(7) cells in the total blood pool. t(14;18)-positive cells seem to be immortalized, but the biological consequences of the other aberrations in positive healthy persons have not been studied in detail. Due to the high frequency of positive individuals, most of them will not suffer from the correspondent leukemia or lymphoma, and criteria for subgroups that may be at a higher risk remain to be determined. Most likely, the number of genetic aberrations in healthy individuals, which so far are only associated with hematopoietic disorders, will increase in the near future.
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PMID:Leukemia- and lymphoma-associated genetic aberrations in healthy individuals. 1190 85

Blood-cell cancers (leukaemias, lymphomas and myeloma) are a very diverse group of neoplasms derived from a variety of stem cells at different hierarchical levels of haemopoietic and lymphoid cell development. This biological heterogeneity is likely to be associated with a variety of different etiological mechanisms. Correspondingly, a large number of inherited normal allelic variations might be expected to contribute to risk. Leukaemias alone have more than 200 different acquired (non-constitutive) molecular abnormalities but some are much more prevalent than others and are associated with biological subtypes with distinctive clinical or prognostic features. Balanced chromosome translocations are very common, together with simple gains or losses of chromosomes. Gene deletions and mutations are also relatively common, especially in more advanced disease. In several types of leukaemia and lymphoma, a transition from benign to malignant status can be tracked together with concurrent accrual of additional molecular abnormalities (e.g. chronic myeloid leukaemia evolving into blast crisis and follicular lymphoma becoming diffuse). The covert preclinical natural history of paediatric leukaemia has been revealed by 'back-tracking' using chromosomal translocation-gene-rated fusion gene sequences as clone-specific stable, specific and sensitive markers. Studies in identical twins, in archived neonatal blood spots of patients and in normal newborn cord bloods all support the contention that chromosomal translocations often initiate leukaemia in utero. Twin concordance rates (and animal modelling) suggest that further secondary genetic changes and exposures postnatally are, however, critical and this is endorsed by the finding that leukaemic fusion genes are present in normal newborn infants at a rate that far exceeds the cumulative risk of leukaemia. The natural history of leukaemic subtypes provides a useful framework for molecular epidemiological studies and significant advances have been made in this respect with infant and childhood acute lymphoblastic leukaemia.
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PMID:Biological models for leukaemia and lymphoma. 1505 6

Fibromodulin is an extracellular matrix protein normally produced by collagen-rich tissues; the fibromodulin gene has been found to be the most overexpressed gene in B-cell chronic lymphocytic leukemia. In this study, fibromodulin was expressed at the gene level (reverse transcription-polymerase chain reaction [RT-PCR]) in all patients with B-CLL (n = 75) and in most (5 of 7) patients with mantle cell lymphoma (MCL). No mutations in the fibromodulin gene were detected. Fibromodulin was also detected at the protein level in the cytoplasm of the B-CLL cells and in the supernatant after in vitro cultivation, but not at the cell surface. Fibromodulin was not found in patients with T-cell chronic lymphocytic leukemia (T-CLL), B-cell prolymphocytic leukemia (B-PLL), T-cell prolymphocytic leukemia (T-PLL), hairy cell leukemia, follicular lymphoma, lymphoplasmacytic lymphoma, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), or chronic myelogenous leukemia (CML) or in 36 hematologic cell lines. Normal blood mononuclear cells (T and B lymphocytes, monocytes), tonsil B cells, and granulocytes did not express fibromodulin. Activation (phorbol 12-myristate 13-acetate [PMA]/ionomycin) of normal T and B lymphocytes induced weak fibromodulin gene expression, but not to the extent seen in freshly isolated B-CLL cells. The reason for the exclusive ectopic expression of fibromodulin in B-CLL and MCL is unknown. However, its unique protein expression makes it likely that fibromodulin is involved in the pathobiology of B-CLL and MCL.
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PMID:Fibromodulin, an extracellular matrix protein: characterization of its unique gene and protein expression in B-cell chronic lymphocytic leukemia and mantle cell lymphoma. 1574 Dec 14

Over the last decade molecular diagnostics technology has developed dramatically from the most laborious, time- consuming southern blot methodology through the revolution of polymerase chain reaction PCR technology to the most reliable, fast, and contamination free molecular analyzer, the real-time quantitative-PCR. The Section of Hematology, Department of Pathology and Laboratory Medicine at King Faisal Specialist Hospital and Research Center has shared this experience during the last 10 years with more than 6,546 samples submitted for the analysis of different gene rearrangements, fusion gene transcripts and gene mutations including Ig heavy chain gene rearrangement for B-cell malignancies, T-cell receptor gamma chain gene rearrangement for T-cell malignancies, BCR/ABL-P210 and P190 fusion gene transcripts, for chronic myeloid leukemia and Philadelphia positive acute lymphoblastic leukemia, PML/RARalpha fusion gene for promyelocytic leukemia, AML1/ETO for acute myeloid leukemia AML-M2 with t8;21, CBFB/MYH11 for AML M4E0 with inv 16, BCL-2 for follicular lymphoma, and BCL-1 for mantle cell lymphoma. Hence, most molecular assays are qualitative in nature, quantitative assays are deemed necessary in the monitoring and follow-up of minimal residual disease in leukemia and lymphoma, and proved in our experience to serve as an essential tool to confirm complete remission CR post-chemotherapy and bone marrow transplantation, and to detect signs of early relapse for proper clinical intervention. In this manuscript, we retrospectively review our experience in molecular hematology and propose our recommended guidelines at King Faisal Specialist Hospital and Research Center.
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PMID:Molecular hematology. Qualitative to quantitative techniques. 1622 48

Contamination of autologous graft by tumor, in addition to incomplete tumor eradication, can partly explain why relapse remains the commonest cause of treatment failure after autologous stem cell transplantation (ASCT) in patients with malignant hematologic disorders. Monitoring of minimal residual disease (MRD) is now recognized as an important diagnostic tool for assessment either of the response to treatments aimed at maximal cytoreduction and the individual risk of relapse. In order to improve cure rates, many strategies to achieve in vivo or in vitro reduction, if not eradication, of residual disease have been proposed. We discuss the significance of MRD and the role of purging in the ASCT setting, focusing on acute myeloid leukemia, chronic myeloid leukemia, multiple myeloma and follicular lymphoma.
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PMID:The significance of minimal residual disease in stem cell grafts and the role of purging: is it better to purge in vivo or in vitro? 1626 60

As part of our routine work-up in the diagnosis of lymphoproliferative disease, we used a rapid polymerase chain reaction (PCR) assay to amplify the DNA fragments of the framework 3 (FR3) region of the immunoglobulin heavy (IgH) chain genes. The assay does not involve hybridization, nested priming, or sequencing of the amplified PCR product. It was performed on 66 specimens of B-cell lymphoproliferative disease, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, multiple myeloma, hairy cell leukemia and follicular lymphoma. Twenty-six specimens of negative controls, including acute myeloid leukemia, chronic myeloid leukemia in myeloid transformation and idiopathic thrombocytopenic purpura, were also analyzed. The assay was performed with 77% sensitivity and 100% specificity. The standard IgH chain gene rearrangement by Southern blot analysis is reserved for the remaining negative cases if clinically indicated.
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PMID:Application of polymerase chain reaction to detect rearrangement of immunoglobulin heavy chain genes in lymphoproliferative disease. 1735 88

The same progress in the recent therapeutic strategy for older adults with hematological malignancies has also been seen in younger adults. The standard initial therapy for elderly acute promylocytic leukemia is the combination with all-trans retinoic acid and anthracyclines. For other acute myeloid leukemias (AML), many trials of combination chemotherapy have not improved the outcome of elderly patients. Gemtuzumab ozogamicin,which is an immunoconjugate binding to CD 33 on the surface of AML blasts, has produced good results for elderly patients in either monotherapy or in combination with conventional chemotherapeutic drugs. One of the BCR-ABL tyrosine kinase inhibitors, imatinib mesylate, is active for elderly Philadelphia-positive leukemia including acute lymphoblastic leukemia and chronic myeloid leukemia. In the treatment of elderly diffuse large B cell lymphoma, combination of rituximab and cyclophosphamide+doxorubicin+vincristine+prednisone (CHOP) has become the therapy of choice based upon a Groupe d'Etude des Lymphomes de l'Adulte (GELA) trial even though there are some other trials for elderly patients such as dose-dense CHOP therapy. For follicular lymphoma, combination therapies of rituximab and cytotoxic drugs such as R-CHOP and R-CVP are also considered as promising therapies. For the management of multiple myeloma, high-dose chemotherapy, mainly melphalan with autologous stem cell transplantation, has become the standard treatment even for elderly patients less than 65 years of age.
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PMID:[Hematological malignancies]. 1735 25

Recently, the standard treatments for hematological malignancies have shown dramatic improvement. For chronic myeloid leukemia, imatinib has become the treatment of choice in initial treatment, and its long-term effectiveness and safety have been confirmed. For acute myelogenous leukemia, cytarabine with anthracycline agent is believed to be the standard treatment in first remission induction therapy. To improve the efficacy of the first remission induction chemotherapy, the addition of gemutuzumab ozogamicin has been investigated intensively all over the world. However, there are many obstacles to conducting its clinical trial in Japan. The addition of rituximab to CHOP improves the survival of patients with diffuse large B-cell lymphoma. For follicular lymphoma patients, rituximab with conventional chemotherapies are considered the standard treatments, but the question of which conventional chemotherapy is better is unsolved. MP therapy had long been the standard treatment for elderly patients with multiple myeloma, but MP therapy plus thalidomide with MP therapy has been found to be superior. In patients who are candidates for autologous stem-cell transplantation, VAD therapy or high-dose dexamethasone therapy followed by autologous stem-cell transplantation is considered the treatment of choice. But the number of transplantations and the timing of second transplantation need more investigation. Considering the overall situation with regard to the standard treatments of hematological malignancies in Japan, there is little difference in practice from western countries. However, the framework of conducting clinical trials to investigate standard treatment in Japan is unsatisfactory.
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PMID:[The standard treatments for patients with hematological malignancies in Japan]. 1749 42

Immunohistochemical determination of p63 protein is frequently used in the pathologic diagnosis of nonhematological solid tumors. In malignant hematological disease, p63 expression has been reported in 22% of follicular lymphoma, about 35% of diffuse large B-cell lymphoma, 23% of chronic lymphocytic leukemia, and in some cases of blast crisis of chronic myelogenous leukemia. Anaplastic large cell lymphoma is a rare disease that accounts for less than 5% of all cases of non-Hodgkin's lymphoma. There is little information concerning p63 expression in this specific type of lymphoma. In some cases, the morphological and phenotypic features between anaplastic large cell lymphoma and classical Hodgkin's lymphoma are similar, making this differential diagnosis challenging. We studied p63 expression using a tissue microarray approach in 154 cases of anaplastic large cell lymphoma, including 38% anaplastic large cell kinase positive and 62% anaplastic large cell kinase negative, and 58 Hodgkin's lymphoma cases. Sixty-eight cases of anaplastic large cell lymphoma (44%) showed p63 nuclear positivity (41% of anaplastic large cell kinase positive and 47% of anaplastic large cell kinase negative). Of 130 cases of systemic-anaplastic large cell lymphoma, 42% showed p63 positivity. The neoplastic cells expressed p63 in 38% of the cases of CD45-negative/anaplastic large cell kinase-negative null cell-type anaplastic large cell lymphoma, a subgroup that offers the most difficulties in the differential diagnosis with classical Hodgkin's lymphoma. In contrast, none of the cases of classical Hodgkin's lymphoma demonstrated any p63 expression. These results demonstrate that p63 protein expression is frequently expressed in a subset of anaplastic large cell lymphoma cases and may be used as a potential tool in the differential diagnosis between anaplastic large cell lymphoma and classical Hodgkin's lymphoma.
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PMID:Expression of p63 in anaplastic large cell lymphoma but not in classical Hodgkin's lymphoma. 1862 Jul 33


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