Tumour stem cells and drug resistance.

Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA.
Nature reviews. Cancer (Impact Factor: 37.91). 05/2005; 5(4):275-84. DOI: 10.1038/nrc1590
Source: PubMed

ABSTRACT The contribution of tumorigenic stem cells to haematopoietic cancers has been established for some time, and cells possessing stem-cell properties have been described in several solid tumours. Although chemotherapy kills most cells in a tumour, it is believed to leave tumour stem cells behind, which might be an important mechanism of resistance. For example, the ATP-binding cassette (ABC) drug transporters have been shown to protect cancer stem cells from chemotherapeutic agents. Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might therefore lead to new therapeutic targets and better anticancer strategies.

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    ABSTRACT: ABSTRACT Objectives:Acute lymphoblasstic leukemia (ALL) is the most common childhood malignancy. Prominin‑1 is a cell‑surface trans‑membrane glycoprotein expressed on the stem cell surface and has potential role in diagnostic and prognostic work‑up of several stem cell cancers. Aim of this Work:To assess the prognostic value of Prominin‑1 expression in Egyptian children with ALL. Subjects and Methods:This study was conducted on 80 Egyptian children with newly diagnosed ALL and 30 healthy children of matched age and sex as a control group. Patient history, and clinical and laboratory examination results were taken, including complete blood count, serum LDH, bone marrow aspiration with cytochemistry, immunophenotyping, FluorescentIn Situ Hybridization technique for detection of t(9;22) and Flow cytometery for estimation of Prominin‑1 expression on blast cells. Results:No statistically significant differences were observed between Prominin‑1 positive and negative patients regarding age, sex and clinical presentation at diagnosis. No statistically significant differences between Prominin‑1 positive and negative patients were observed regarding white blood cells and platelet counts, peripheral blood and bone marrow blast cells percentage while there were significantly higher hemoglobin and LDH levels in Prominin‑1 positive patients. There were no significant differences between Prominin‑1 positive and negative patients regarding immunophenotyping and t(9;22). There were statistically significant differences in disease outcome between Prominin‑1 positive and negative expression with higher rate of relapse and death and lower rate of complete remission in patients with Prominin‑1 positive expression (14 cases with Prominin‑1 positive relapsed versus 2 cases with Prominin‑1 negative, 12 cases with Prominin‑1 positive died versus 2 cases with Prominin‑1 negative and complete remission occurred in 20 cases with Prominin‑1 positive versus 30 cases with Prominin‑1 negative) (P = 0.017). There was statistically significant difference in disease‑free survival (P = 0.0072) and overall survival (P = 0.0424) between ALL patients with Prominin‑1 positive and Prominin‑1 negative expression. Conclusion:Prominin‑1 is a helpful prognostic marker in patients with ALL; therefore, it should be routinely assessed at diagnosis in ALL patients for better prognostic assessment and should be taken in consideration in designing future therapeutic strategies based on patient‑specific risk factors.


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