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)

Thirty-two adult patients with acute leukemia were treated with continuous infusion carboplatin and etoposide at eight different dose levels. Dose limiting toxicity was encountered at doses of carboplatin of 310 mg/m2 per day for 5 days (total 1550 mg/m2 per course) and etoposide 150 mg/m2 per day for 5 days (total dose 750 mg/m2 per course) and consisted primarily of gastrointestinal toxicity. Of the five courses given at the highest dose level, three were complicated by grade 4 gastrointestinal toxicity. The recommended dose for further phase II evaluations in acute leukemia is carboplatin 250 mg/m2 per day for 5 days by continuous infusion and etoposide 150 mg/m2 per day for 5 days given by continuous infusion. The response to treatment was notable for a single complete remission achieved in a patient with acute undifferentiated leukemia. None of the patients with chronic myeloid leukemia in blast crisis (n = 12) or with acute lymphocytic leukemia (n = 4) or acute myeloid leukemia (AML) (n = 15) achieved complete remission (CR), although all patients with AML entered on this trial had prior complete remissions that were less than 1 year in duration, and many were refractory, either to primary therapy or to the most recent attempt to obtain CR.
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PMID:A phase I trial of carboplatin and etoposide given as continuous infusions to adults with leukemia. 809 41

A large number of continuous human leukemia cell lines have been established over the last three decades. Clearly, leukemia cell lines have become important research tools. Here, we have summarized the immunological, molecular and standard cytogenetic features of a panel of well characterized B cell precursor (BCP)-leukemia cell lines which were derived from patients with acute lymphoblastic/undifferentiated leukemia (ALL/AUL) or chronic myeloid leukemia (CML) in blast crisis. Following the recently proposed immunological EGIL classification, we assigned our panel of 27 BCP-cell lines to one of the following categories: B-I pro-B cell line; B-II common-B cell line; and B-III pre-B cell line. All cell lines express general B-lineage associated surface markers (HLA-DR, CD22, CD79a) being negative for surface immunoglobulin (Ig); the differences between the subgroups reside in expression of CD10 and cytoplasmic Ig. Several BCP-cell lines show the myelomonocytic cell-associated markers CD13 and/or CD33. These immunologically 'biphenotypic' BCP-cell lines are generally TdT+ CD10+ CD13+ CD19+ CD22+ CD34+ and carry the Philadelphia (Ph) translocation. The BCP-cell lines display surface receptors for interferon-gamma (CD119), interleukin-7 (CD127) and FLT-3 ligand (CD135). All BCP-cell lines examined have complex numerical and structural chromosomal alterations including translocations commonly seen in BCP-ALL such as t(4;11), t(9;22), t(11;19), t(12;21), and t(17;19) involving the fusion genes MLL-AF4, BCR-ABL, ENL-MLL, TEL/ETV6-AML1 and E2A-HLF, respectively. Besides the expected rearrangement of the Ig heavy chain receptor gene, several cell lines also have rearrangements of the T cell receptor genes beta, gamma or delta. While some BCP-cell lines express (aberrantly) myeloperoxidase at the mRNA level, most lines are negative in the immunological or cytochemical staining. Several large series documented the difficulty in establishing such BCP cell lines with success rates in the range of 10-20% (on average 15%). Still, since the establishment of the first bonafide BCP-cell line in 1974 (cell line REH), some 150 cell lines have been established of which, however, only a small percentage have been sufficiently well characterized and described. A higher success rate for immortalizing any given leukemia cell might depend on a closer emulation of the physiological in vivo microenvironment. The possibility to grow in vitro leukemia cells at will would represent ideal experimental systems permitting basic research and patient-specific investigations. In summary, the use of well-characterized BCP-cell lines provide unprecedented opportunities for studying a multitude of biological aspects related to normal and neoplastic B-lymphocytes.
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PMID:Establishment and characterization of human B cell precursor-leukemia cell lines. 968 Jan 6

The present study was undertaken to ascertain the frequency of cytogenetic polyclonality in various hematologic malignancies and to investigate whether morphologic subgroup, age, gender, or previous genotoxic exposure influences the incidence. Among 2,243 cytogenetically investigated hematologic malignancies, 10 acute myeloid leukemias (AML), 5 myelodysplastic syndromes (MDS), 2 acute lymphoblastic leukemias (ALL), 1 acute undifferentiated leukemia (AUL), 1 atypical Philadelphia chromosome-negative (Ph-) chronic myeloid leukemia (CML), 1 chronic myeloproliferative disorder (CMD), and 1 chronic lymphoproliferative disorder (CLD) with karyotypically unrelated clones were identified, constituting 2.6% of AML, 1.6% of MDS, 0.8% of ALL, 13% of AUL, 9.1% of Ph- CML, 1.5% of CMD, and 2.8% of CLD with chromosomal abnormalities. In contrast to the cytogenetic features, the X-inactivation pattern was monoclonal in the two informative female patients that could be investigated. Among 17,733 karyotypically aberrant published cases surveyed, significant frequency differences (P < 0.001) were discerned: 1.7% of 6,526 AML, 3.4% of 2,391 MDS, 0.4% of 1,920 Ph+ CML, 2.9% of 856 CMD, 0.9% of 4,226 ALL, and 5.8% of 1,814 CLD displayed unrelated clones. The incidence of cytogenetic polyclonality did not differ significantly among the MDS, CMD, or ALL subgroups, between males and females, between children (< 16 years) and adults, or between B- and T-cell ALL, whereas the frequencies varied among the AML FAB types (P < 0.05), among the different CLD entities (P < 0.001), and between B- and T-cell CLD (P < 0.001). Furthermore, the incidence was higher in therapy-related AML and MDS than in de novo AML and MDS (P < 0.001 and P < 0.01, respectively).
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PMID:Cytogenetic polyclonality in hematologic malignancies. 1045 2

Chronic myelogenous leukemia was diagnosed in a 3.5-year-old neutered male Golden Retriever. The diagnosis was based on persistent leukocytosis (>73.0X10(3)/microliter), composed of a proportionate left shift to progranulocytes with no evidence of underlying inflammation, infection, or neoplasia. Marked dysplasia was evident in neutrophils and platelets in peripheral blood. Bone marrow and splenic aspirates were dominated by mature and immature neutrophils with < 2% myeloblasts. Cytochemical and flow cytometric assays confirmed that cells in the peripheral blood and spleen were of committed neutrophil lineage. The dog responded initially to treatment with hydroxyurea, but developed acute undifferentiated leukemia approximately 83 days after initial presentation.
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PMID:Diagnosis of chronic myelogenous leukemia in a dog using morphologic, cytochemical, and flow cytometric techniques. 1202 26


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