Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the development of highly effective treatment strategies for acute promyelocytic leukaemia around 10% of patients die in the presentation period as a consequence of the associated bleeding diathesis. The cause of the coagulopathy is complex resulting from a combination of tissue factor (TF) and cancer procoagulant (CP) induced disseminated intravascular coagulation, exaggerated fibrinolysis due predominantly to enhanced expression of annexin II on APL blast cell membranes and blast cell production of cytokines. All-trans retinoic acid (ATRA) has revolutionised the treatment of APL. When combined with chemotherapy long term survival rates of up to 80% can be achieved. Commencement of ATRA induces APL blast cell differentiation and is associated with a rapid resolution of the bleeding tendency through a combination of effects which include up regulation of thrombomodulin and down regulation of TF and CP production and cell surface expression of annexin II.
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PMID:Haemostatic problems in acute promyelocytic leukaemia. 1675 74

Acute leukemia may be associated with coagulopathy, predominantly severe bleeding diathesis caused by disseminated intravascular coagulation (DIC) and/or hyperfibrinolysis. Disordered hemostasis is characteristic for acute promyelocytic leukemia (APL, FAB M3). However, thromboembolic events such as arterial occlusion localized to the large vessels at presentation is very rare and almost exclusively linked to APL. We report a case of severe recurrent acute arterial thromboembolism at presentation in AML FAB M1. Most likely, the ischemic events in our patient resulted from leukemia as the thrombus material included many leukemic blasts. The thrombotic complications resulted in leg amputation in this patient. Despite leg amputation just a couple of hours before and extremely high infectious risk of the patient, chemotherapy was administered. The clinical course of cessation of the ischemic events and a fast reduction of the blasts in the peripheral blood smear after chemotherapeutic treatment of the patient outlines the importance and life saving role of early chemotherapy even under adverse circumstances.
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PMID:AML M1 presenting with recurrent acute large arterial vessel thromboembolism. 1701 Oct 31

Recently, we have reported that 3-hydrogenkwadaphnin (3-HK), a diterpene ester isolated from Dendrostellera lessertii (Thymealeaceae), is very effective against leukemia cell lines without any detectable effects on normal cells (Moosavi et al., 2005b). In this study, we report that 3-HK induces G1 cell-cycle arrest, differentiation and apoptosis in APL NB4 cell line. Indeed, the drug between 24 to 96 h induced 7-65% growth inhibition of NB4 cells. Cell viability was also decreased by 2-55% between 24 to 96 h treatments with the drug, respectively. These effects of the drug were also dose-dependent. According to flow cytomtry results, 3-HK (15 nM) induced a significant G1-arrest up to 24 h which was consequently followed with appearance of sub-G(1) peak at 72 to 96 h. Hoechst 33258 staining and DNA fragmentation assays confirmed the occurrence of apoptosis among the treated cells. On the other hand, NBT reducing assay, Wright-Giemsa staining, phagocytic activity and expression of cell surface markers (CD11b and CD14) confirmed that the inhibition of proliferation is associated with differentiation especially toward macrophage-like morphology. Interestingly, 3-HK at 5 and 10 nM enhanced the effects of all-trans retinoic acid (ATRA) in NB4 cells. Based on these results, 3-HK might become an ideal candidate for treatment of APL patients pending full exploration of its biological functions.
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PMID:3-Hydrogenkwadaphnin induces monocytic differentiation and enhances retinoic acid-mediated granulocytic differentiation in NB4 cell line. 1712 8

The annual incident rate of pediatric acute myeloid leukemia (AML) is now 10 per million in Japan, against 5 to 9 per million in the USA and Europe. Overall long-term survival has now been achieved for more than 50% of pediatric patients with AML in the USA and in Europe. The prognostic factors of pediatric AML were analyzed,and patients with AML were classified according to prognostic factors. The t(15;17), inv(16) and t(8;21) have emerged as predictors of good prognosis in children with AML. Monosomy 7, monosomy 5 and del (5 q) abnormalities showed a poor prognosis. In addition to chromosomal deletions, FLT 3/ITD identifies pediatric patients with a particularly poor prognosis. Clinical trials of AML feature intensive chemotherapy with or without subsequent stem cell transplantation. Risk group stratification is becoming increasingly important in planning AML therapy. APL can be distinguished from other subtypes of AML by virtue of its excellent response and overall outcome as a result of differentiation therapy with ATRA. Children with Down syndrome and AML have been shown to have a superior prognosis to AML therapy compared to other children with AML. The results of the Japan Cooperative Study Group protocol ANLL 91 was one of the best previously reported in the literature. With the consideration of quality of life (QOL), risk-adapted therapy was introduced in the AML 99 trial conducted by the Japanese Childhood AML Cooperative Study Group. A high survival rate of 79% at 3 years was achieved for childhood de novo AML in the AML 99 trial. To evaluate the efficacy and safety of the treatment strategy according to risk stratification based on leukemia cell biology and response to the initial induction therapy in children with AML, the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) has organized multi-center phase II trials in children with newly diagnosed AML.
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PMID:[Acute myeloid leukemia]. 1730 20

The study was purposed to explore the correlation between apoptosis-related gene pnas-2 and leukemia. The RT-PCR was performed to detect the expression levels of pnas-2 gene in NB4, K562, U937 cells before and after treatment with AS(4)S(4), and to analysis the expression change of pnas-2 gene in bone marrow cells from patients with acute leukemia before and after chemotherapy. The results showed that the expression of pnas-2 gene in arsenic sulfide treated NB4 cells was down regulated in time-dependent manner, but the same outcome in K562 and U937 cells after being treated with AS(4)S(4) was not found. The positive expression rate of pnas-2 in cells from untreated patients with acute leukemia was 100%, and was significantly higher than that in normal control group. After chemotherapy, the expression was negative in complete remission patients, whereas in no-remission patients there were no significant differences of expression of pnas-2 before and after treatment. It is concluded that the pnas-2 gene may be closely related with apotosis of arsenic sulfide treated APL cells, and may consider as a molecular biological remission marker in acute leukemia.
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PMID:[Correlation between expression of apoptosis-related gene pnas-2 and leukemia]. 1770 94

The study was aimed to explore whether there are leukemic characteristics in the bone marrow mesenchymal stem cells (BMMSC) from leukemic patients as compared with normal controls. The mesenchymal stem cells from bone marrow of normal volunteers and patients with APL and CML were isolated, then cultured and proliferated in vitro. The morphology, growth curve and cell surface markers of two different sources mesenchymal stem cells were investigated for detecting whether the bone marrow mesenchymal stem cells derived from leukemia patients have the specific abnormal fusion gene of leukemia cells through fluorescent in situ hybridization. The results indicated that there was no significant difference between the mesenchymal stem cells derived from different subjects, the bone marrow mesenchymal stem cells derived from leukemia patients did not have the clonal malignant fusion gene as seen in the leukemia cells. Taken altogether, mesenchymal stem cells derived from leukemia patients had no biological differences as compared with those from normal volunteers, and no malignant clonal abnormality was found. It is concluded that mesenchymal stem cells derived from leukemia patients as an alternative vehicle may be used for assistant of autologous hematopoietic stem cell transplantation or cell therapy and gene therapy.
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PMID:[Are leukemic patient bone marrow mesenchymal stem cells malignant?]. 1795 60

To analyze the prognosis and risk factors of acute nonlymphocytic leukemia (ANLL), 94 patients with acute nonlymphocytic leukemia were enrolled in this study, while survival rate and risk factors of prognosis were analyzed. The results indicated that the complete remission (CR) ratio was 51.1%. Overall survival and event-free survival rates of month 6, 12, 18, 24 were 68.6%, 55.8%, 53.8%, 46.4%, 21.3% and 57.9%, 38.6%, 33.3%, 31.6%, 0% respectively. The factors such as age<40 years, WBC<10.0x10(9)/L before chemotherapy, WBC in the period of bone marrow suppression<1.0x10(9)/L, chemotherapy within 1 month after occurrence of leukemia, blood transfusion before chemotherapy of APL had favourable influence on remission and survival rates of ANLL patients. CR1, the time to get CR, length of CR and relapse significantly correlated with prognosis (p<0.05). It is concluded that the individualized therapy concerning the risk factors should be applied to ANLL patients for improving the remission, survival rate and prognosis.
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PMID:[Analysis on prognosis and correlative factors of acute nonlymphocytic leukemia]. 1808 89

5' nucleotides (5'NT), a purine degradative enzyme, is capable of hydrolyzing nucleotide and acting as a phosphotransferase simultaneously. It has critical role in maintaining nucleotide metabolism balance. The present study was aimed to investigate the expression of 5'NT in bone marrow granulocytes (BMGs) from patients with acute myeloid leukemia (AML) and healthy donors comparatively. The BMGs were isolated from bone marrow of 33 patients with AML and 6 healthy donors by using lymphocyte isolating solution. The reactivity of 5'NT was detected by electron microscope and cytochemistry of cytidine monophosphate (CMP). The positive BMG ratio and their index were calculated on the base of ultrastructural observation semiquantitatively. The results indicated that electron microscopy revealed plasma membrane reacting pattern of CMP. Most BMGs from normal donors were CMP negative or exhibited lower active degree. All cases of M(0), M(1), M(2) and t (8; 21) showed high positive percentages and high indexes of BMGs, but no statistic differences between them. APL of t (15; 17) shared lower percentages and indexes than other subtypes. There was no significant difference between APL and normal donors statistically. In conclusions, the results suggested the expression of 5'NT may be associated with BMG differentiation in AML, and APL of t (15; 17) may be a highly differentiated leukemia subtype.
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PMID:[Ultrastructural analysis of 5' nucleotides distribution in acute myeloid leukemia subtypes]. 1854 13

Therapy-related acute promyelocytic leukemia (t-APL) with t(15;17) translocation is a well-recognized complication of cancer treatment with agents targeting topoisomerase II. However, cases are emerging after mitoxantrone therapy for multiple sclerosis (MS). Analysis of 12 cases of mitoxantrone-related t-APL in MS patients revealed an altered distribution of chromosome 15 breakpoints versus de novo APL, biased toward disruption within PML intron 6 (11 of 12, 92% vs 622 of 1022, 61%: P = .035). Despite this intron spanning approximately 1 kb, breakpoints in 5 mitoxantrone-treated patients fell within an 8-bp region (1482-9) corresponding to the "hotspot" previously reported in t-APL, complicating mitoxantrone-containing breast cancer therapy. Another shared breakpoint was identified within the approximately 17-kb RARA intron 2 involving 2 t-APL cases arising after mitoxantrone treatment for MS and breast cancer, respectively. Analysis of PML and RARA genomic breakpoints in functional assays in 4 cases, including the shared RARA intron 2 breakpoint at 14 446-49, confirmed each to be preferential sites of topoisomerase IIalpha-mediated DNA cleavage in the presence of mitoxantrone. This study further supports the presence of preferential sites of DNA damage induced by mitoxantrone in PML and RARA genes that may underlie the propensity to develop this subtype of leukemia after exposure to this agent.
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PMID:Molecular analysis of t(15;17) genomic breakpoints in secondary acute promyelocytic leukemia arising after treatment of multiple sclerosis. 1865 Apr 49

Nested reverse-transcriptase polymerase chain reaction (rt-PCR) was performed on 58 leukemia patients at BIRDEM Laboratory, as a pioneering work in Bangladesh. Thirty of themwere examined for the presence of BCR-ABL being clinically and morphologically diagnosed as chronic myeloid leukemia (CML) and 28 for PML-RARalpha fusion transcripts being clinically and morphologically diagnosed as acute promyelocytic leukemia (APL/ AML M3). The cases were selected for targeted therapy with imatinib mesylate and all-Trans retinoic acid (ATRA) to treat CML and APL respectively. Samples were received either before commencement or during therapy. In the positive cases, amplified DNA products were visible after gel electrophoresis and were reported accordingly. In case of BCR-ABL, positive results were found for five out of six (83.33%) untreated cases and 11 out of 24 (45.83%) treated cases. Positive results for PML-RARalpha were found for 12 out of 14 (85.70%) untreated cases and 11 out of 16 (68.75%) treated cases. A strong positive correlation was found between duration of treatment and negativity of PCR results in both the cases. In present times, the detection of minimal residual disease in patients undergoing treatment for hematological malignancies has become an important goal, not only to monitor the effectiveness of therapy but also to detect an impending relapse. This is the first time in Bangladesh that rt-PCR method is being employed to detect or monitor the presence of abnormal fusion genes in hematological malignancies.
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PMID:Rt-PCR method for diagnosis and follow-up of hematological malignancies: first approach in Bangladesh. 1878 70


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