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Emergence of genetic instability in children treated for leukemia

SCIENCE 2000年第5465期288卷 514-517页

作者： Finette, BA Homans, AC Albertini, RJ Univ Vermont Dept Pediat Burlington VT 05405 USA Univ Vermont Dept Microbiol & Mol Genet Burlington VT 05405 USA Univ Vermont Vermont Canc Ctr Burlington VT 05405 USA Univ Vermont Dept Med Burlington VT 05405 USA

T cells from patients who had received chemotherapy for B-lineage acute lymphocytic Leukemia were studied to determine whether genetic instability, a principal characteristic of cancer cells, can also occur in nonmalignant cells. Consistent with expectations for a genetic instability phenotype, multiple mutations were detected in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) reporter gene in independently isolated mutant T cells expressing identical rearranged T cell receptor beta (TCR beta) gene hypervariable regions. These results indicate that cancer treatment can lead to genetic instability in nonmalignant cells in some individuals. They also suggest a mechanistic paradigm for the induction of second malignancies and drug resistance.

关键词：等位基因抗肿瘤药/治疗应用伯基特淋巴瘤/血液伯基特淋巴瘤/药物疗法伯基特淋巴瘤/遗传学细胞谱系细胞转化肿瘤克隆细胞抗药性肿瘤基因重排 β链T细胞抗原受体基因报告基因 T细胞受体次黄嘌呤磷酸核糖转移酶/遗传学突变肿瘤继发原发性/病因学前体细胞淋巴母细胞白血病淋巴瘤/血液前体细胞淋巴母细胞白血病淋巴瘤/药物疗法前体细胞淋巴母细胞白血病淋巴瘤/遗传学复发 T淋巴细胞青少年成年人儿童儿童学龄前人类婴儿

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Cysteine chloromethyl and diazomethyl ketone derivatives with potent anti-leukemic activity

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 2000年第6期10卷 547-549页

作者： Perrey, DA Narla, RK Uckun, FM Parker Hughes Inst Parker Hughes Canc Ctr St Paul MN 55113 USA

A series of cysteine diazomethyl- and chloromethyl ketone derivatives has been synthesized and evaluated against human B-lineage (Nalm-6) and T-lineage (Molt-3) acute lymphoblastic leukemia cell lines. The chloromethyl ketone compounds showed potent cytotoxicity against these cell lines, with IC50 values in the low micromolar range. The best compounds were N-acetyl-S-dodecyl-Cys chloromethyl ketone (IC50 = 2.0 mu M against Nalm-6, 2.3 mu M against Molt-3) and N-acetyl-S-trans,trans-farnesyl-Cys chloromethyl ketone (IC50 = 3.0 mu M against Nalm-6 and 1.4 mu M against Molt-3). (C) 2000 Elsevier Science Ltd. All rights reserved.

关键词：氨基酸氯甲基酮类/化学合成氨基酸氯甲基酮类/药理学抗肿瘤药/化学合成抗肿瘤药/药理学细胞系着色剂半胱氨酸/类似物和衍生物半胱氨酸/化学合成半胱氨酸/药理学前体细胞淋巴母细胞白血病淋巴瘤/药物疗法四唑鎓盐类噻唑类肿瘤细胞培养的肿瘤抑制蛋白质p53/代谢人类

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The S-alkyl chain length as a determinant of the anti-leukemic activity of cysteine chloromethyl ketone compounds

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 2000年第6期10卷 551-552页

作者： Perrey, DA Scannell, MP Narla, RK Uckun, FM Parker Hughes Inst Parker Hughes Canc Ctr St Paul MN 55113 USA

A series of cysteine chloromethyl ketone compounds with a systematic variation of the S-alkyl chain length have been synthesized in order to gauge the effect of the alkyl chain length on the cytotoxicity of these compounds against human acute lymphoblastic leukemia cells. Comparable activities were observed for compounds with S-alkyl chains ranging from pentyl to dodecyl, with the best being undecyl (IC50 = 1.7 mu M) and dodecyl (IC50 = 2.0 mu M) against B-lineage leukemia cells and hexyl (IC50 = 0.7 mu M) against T-lineage leukemia cells. (C) 2000 Elsevier Science Ltd. All rights reserved.

关键词：烷化作用抗肿瘤药/化学合成抗肿瘤药/药理学细胞系着色剂前体细胞淋巴母细胞白血病淋巴瘤/药物疗法构效关系四唑鎓盐类噻唑类肿瘤细胞培养的肿瘤抑制蛋白质p53/代谢人类

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Trisomy 5 as a sole cytogenetic abnormality in pediatric acute lymphoblastic leukemia

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CANCER GENETICS AND CYTOGENETICS 2000年第1期118卷 69-71页

作者： Sandoval, C Mayer, SP Ozkaynak, MF Tugal, O Jayabose, S New York Med Coll Dept Pediat Valhalla NY 10595 USA

We describe a case of pediatric acute lymphoblastic leukemia (ALL) with trisomy 5 as a sole cytogenetic abnormality,. A comparison is made with the two cases of adult acute lymphoblastic leukemia with trisomy 5 in the literature. This rare cytogenetic abnormality may por tend an especially poor prognosis in patients with ALL. (C) Elsevier Science Inc., 2000. AII rights reserved.

关键词：染色体人 5对/遗传学致命性结局基因重排 B淋巴细胞/遗传学基因重排 δ链T细胞抗原受体基因免疫球蛋白/遗传学前体细胞淋巴母细胞白血病淋巴瘤/诊断前体细胞淋巴母细胞白血病淋巴瘤/药物疗法前体细胞淋巴母细胞白血病淋巴瘤/遗传学前体细胞淋巴母细胞白血病淋巴瘤/死亡率前体细胞淋巴母细胞白血病淋巴瘤/病理学预后三体性/遗传学成年人儿童女(雌)性人类男(雄)性

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Toxic epidermal necrolysis following combination of methotrexate and trimethoprim-sulfamethoxazole

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INTERNATIONAL JOURNAL OF DERMATOLOGY 2000年第8期39卷 621-623页

作者： Yang, CH Yang, LJ Jaing, TH Chan, HL Chang Gung Mem Hosp Dept Dermatol Taipei 10591 Taiwan Chang Gung Mem Hosp Dept Pediat Div Hematol & Oncol Taipei 10591 Taiwan

A 15-year-old boy with T-cell acute lymphoblastic leukemia (ALL) (FAB L1), diagnosed in 1995, received combination chemotherapy consisting of 6 weeks of induction (vincristine, epirubicin, L-asparaginase, prednisolone) and 2 weeks of consolidation (cytosine arabinosides, etoposide). After achieving remission, for further maintenance of remission, he was treated with 14 cycles of intensive chemotherapy consisting of 6-MP, 10 mg/kg orally on the first 4 days, and cyclophosphamide, 1200 mg/m(2), vincristine, 1.5 mg/m(2), epirubicin, 15 mg/m(2), and cytosine arabinoside, 40 mg/m(2), intravenously on days 4, 11, 39, and 40, respectively. On day 18 of each cycle, he received intravenous methotrexate (MTX) infusion in a total dose of 150 mg/m(2) plus oral leucovorin (30 mg/m(2)) rescue 36 h after starting MTX therapy. In addition, oral trimethoprim-sulfamethoxazole was given regularly to prevent Pneumocystis carinii infection. The patient achieved remission during the first course of treatment, but 8 months later the disease relapsed. He then received four doses of MTX (800 mg intravenously) plus leucovorin rescue in the following 4 months. During the last MTX therapy, small hemorrhagic bullae were found on the lateral side of the right ankle, but subsided after a few days. Due to partial remission of the disease, he was admitted again in January 1999 for high-dose MTX therapy. An initial hemogram on admission revealed hemoglobin 7.2 g/dl, white cell count 15,200/mm(3), platelet count 153/mm(3), blood creatinine 0.5 mg/dL, and alanine leucine aminotransferase (ALT) 20 U/L. He received 8500 mg of MTX (5000 mg/m(2)) as a continuous intravenous infusion for 24 h. Thirty-six hours after the start of MTX infusion, leucovorin (30 mg, intravenous) rescue was initiated every 6 h for 3 days. Another preventive measure to cover MTX toxicity included aggressive intravenous fluid replacement (4 L/m(2)/day) and the addition of 25 meq/L sodium bicarbonate to the intravenous fluid to alk

关键词：抗感染药/副作用抗代谢药抗肿瘤/副作用抗肿瘤联合化疗方案/治疗应用致命性结局甲氨蝶呤/副作用前体细胞淋巴母细胞白血病淋巴瘤/药物疗法 Stevens-Johnson综合征/病因学 Stevens-Johnson综合征/病理学青少年人类男(雄)性

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CEREBRAL INFARCTION IN A PATIENT WITH ACUTE LYMPHOBLASTIC-LEUKEMIA AFTER FRESH-FROZEN PLASMA REPLACEMENT DURING L-ASPARAGINASE THERAPY

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AMERICAN JOURNAL OF HEMATOLOGY 1992年第4期41卷 295-296页

作者： ISHII, H OH, H ISHIZUKA, N MATSUURA, Y NAKAMURA, H ASAI, T YOSHIDA, S Second Dept. of Internal Medicine Chiba University School of Medicine Chiba-City Japan

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小儿急性淋巴细胞型白血病诱导缓解治疗:附21例报告