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At least 721 records · Page 40Linked to original sources

Serologic recognition of a HLA-B44(12) subgroup associated with the 44.2 specificity defined by CML.

Several investigators have reported that subdivisions of HLA-B44, which are not defined by available cytotoxic antisera, can be detected by cytotoxic T lymphocytes. The present study was designed to evaluate two sera which appear to recognize a specificity on some HLA-B44 and B45 positive cells and to determine whether the specificity is correlated with one of the B44 subgroups which are defined by cell-mediated lympholysis. Serum BG1359, eluted from a placenta and serum Cutchember (a gift from Dr. Wilma Bias), were tested on a 23-member B44 positive cell panel. The panel was typed independently with CTLQ1/M3 (specificity 44.1) and CTLM3/Q1 (specificity 44.2). Cells classified as 44.2 usually typed positive with serums 1359 and Cutchember, whereas 44.1 cells usually were negative with these sera in the Amos modified cytotoxicity technique. In the 4th American workshop data, serologic reactivity correlated with B44 (r = 0.87 and 0.75) and B45 (r = 0.32 and 0.34) for serums 1359 and Cutchember, respectively. In a North Carolina population study (N = 155), specificity 1359 was detected in 37 of 53 (70%) of B44 positive individuals and in 5 of 6 B45 positive individuals. In three informative families, the 1359 private specificity segregated with B44 haplotypes. The 44.2 subgroup is in positive linkage disequilibrium with C4 and DR7 and possibly with A23, A26, and A29, whereas the 44.1 subgroup seems to be in disequilibrium with A2, Cw5, DR4, and DRw6.

Cytotoxicity, Immunologic↗

RNAi-mediated knockdown of P-glycoprotein using a transposon-based vector system durably restores imatinib sensitivity in imatinib-resistant CML cell lines.

OBJECTIVE: Resistance to therapeutic drugs is a frequent phenomenon in hematologic malignancies, causing treatment failure in patients with leukemias and lymphomas. Overexpression of the multidrug-resistance gene (MDR-1) and its translational product P-glycoprotein (PgP) represents one mechanism of fatal drug resistance. METHODS: We constructed a nonviral, transposon-based vector system for the stable knockdown of PgP in chronic myeloid leukemia cell lines resistant to imatinib and doxorubicin. RESULTS: Using this strategy, PgP expression was completely knocked down 72 hours after vector inoculation and lasted for several months. Cellular efflux of the PgP substates rhodamine and doxorubicin was abolished. Vector-treated cells were resensitized to imatinib- and doxorubicin-induced cell death. CONCLUSION: Using chronic myeloid leukemia as a model, we show that PgP-mediated resistance to imatinib and anthracyclines can be durably reversed by nonviral, transposon-based knockdown of PgP in malignant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Imatinib mesylate (STI571) for myeloid malignancies other than CML.

Imatinib mesylate, a small molecule tyrosine kinase inhibitor, has had a major impact on the treatment of Philadelphia chromosome positive chronic myelogenous leukemia. This review will explore its potential in the treatment of other myeloid neoplasms, based on its ability to inhibit Kit and PDGFR kinases in addition to Bcr-Abl. Imatinib's potential role in the treatment of Philadelphia chromosome negative chronic myelogenous leukemia, systemic mastocytosis with associated hematologic neoplasms, chronic myelomonocytic leukemia, specific subtypes of acute myelogenous leukemia, myelofibrosis/myeloid metaplasia, and polycythemia vera is discussed.

Benzamides↗

A 2-year-old with atypical CML with a t(5;12)(q33;p13) treated successfully with imatinib mesylate.

Atypical chronic myelogenous leukemia (aCML) is a myelodysplastic/myeloproliferative disorder that usually occurs in older adults. Here we report a pediatric patient with aCML and a t(5;12)(q33;p13) with a corresponding fusion gene ETV6-PDGFRB. Because the PDGFRB tyrosine kinase is one of the known targets of tyrosine kinase inhibitors, this patient achieved cytogenetic and molecular remission with treatment with imatinib mesylate (formerly STI571; now Gleevec in the United States and Glivec in Europe). This case illustrates one of many myelodysplastic/myeloproliferative disorders that can be treated with this particular tyrosine kinase inhibitor.

Benzamides↗

Lymphoid transformation in a CML patient in complete cytogenetic remission following treatment with imatinib.

We describe here a patient with Philadelphia (Ph) chromosome-positive chronic myeloid leukemia who achieved a complete cytogenetic response following treatment with imatinib and then progressed abruptly to lymphoid blastic transformation. The sequence of events suggests that at least in some cases patients who respond well to imatinib may still harbor residual leukemia progenitor or 'stem' cells that are susceptible to acquisition of molecular events that underlie progression to advanced phase disease. The case highlights the need for molecular monitoring of responders and the need to develop strategies for reducing to a minimum or totally eradicating leukemia cells.

Aged↗

Cytotoxic and apoptogenic effect of tea (Camellia sinensis var. assamica) root extract (TRE) and two of its steroidal saponins TS1 and TS2 on human leukemic cell lines K562 and U937 and on cells of CML and ALL patients.

The anticancer activity of di- and tri-terpenes and other polyphenolic compounds present in tea is already reported. We evaluated the cytotoxic and apoptogenic effect of tea root extract (TRE) and two of its steroidal saponins named as TS1 and TS2, on human cell lines and on cells from leukemic patients. It was found that TRE, TS1 and TS2 significantly decreased cell count and that TRE caused apoptosis, as confirmed morphologically by confocal microscopy and by flow-cytometric analysis using Annexin-V FITC and propidium iodide (PI). Cell count and MTT assay in normal white blood cells (WBC) of healthy volunteers revealed that TRE produced insignificant reduction in cell count and cytotoxicity.

Apoptosis↗