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In this study the efficacy of a first\u2010line in vivo therapy was compared with treatment by R\u2010roscovitine (ROSC) alone or by purine analogues (cladribine and fludarabine) combined with maphosphamide for 14 CLL patients under ex vivo conditions. ROSC induced the highest reduction in numbers of living B\u2010cells, coinciding with an increased rate of apoptosis. After 24\u2009h the percentage of apoptotic cells in ROSC\u2010treated cultures was markedly higher than in untreated controls. ROSC also induced strong activation of the apoptosome and effector caspases in CLL cells. During progression of apoptosis the plasma membrane became permeable, resulting in the release of activated caspases into the culture medium. Leukemic cells were more sensitive to ROSC than normal mononuclear cells. Treatment with ROSC did not affect the activating phosphorylation of CDK2 or CDK1. However, ROSC decreased phosphorylation of survivin, CDK7, and RNA\u2010Pol II, resulting in inhibition of transcription elongation and subsequent down\u2010regulation of levels of anti\u2010apoptotic factors, thereby facilitating apoptosis. Unlike ROSC, two other purine analogues barely affected the cellular levels of anti\u2010apoptotic proteins and more weakly activated effector caspases. In addition, the efficacies of in vivo and ex vivo therapies were found to be correlated. Marked between\u2010patient differences in expression patterns of apoptosis\u2010regulating factors in CLL cells were observed, explaining the variations in patients' sensitivity to therapy. J. Cell. Biochem. 109: 217\u2013235, 2010. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.22400","type":"journal-article","created":{"date-parts":[[2009,11,12]],"date-time":"2009-11-12T18:56:41Z","timestamp":1258052201000},"page":"217-235","source":"Crossref","is-referenced-by-count":19,"title":["R\u2010roscovitine (Seliciclib) affects CLL cells more strongly than combinations of fludarabine or cladribine with cyclophosphamide: Inhibition of CDK7 sensitizes leukemic cells to caspase\u2010dependent apoptosis"],"prefix":"10.1002","volume":"109","author":[{"given":"Ma\u0142gorzata","family":"Rogali\u0144ska","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerzy Z.","family":"B\u0142o\u0144ski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oxana","family":"Komina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"G\u00f3ralski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolanta D.","family":"\u017bo\u0142nierczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henryk","family":"Piekarski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadeusz","family":"Robak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zofia M.","family":"Kilia\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f3zefa","family":"W\u0119sierska\u2010G\u0105dek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,11,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00492-1"},{"key":"e_1_2_6_3_1","first-page":"5561","article-title":"Differential scanning calorimetry of nuclei as a test for the effects of anticancer drugs on human chromatin","volume":"49","author":"Almagor M","year":"1989","journal-title":"Cancer Res"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc968"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-07-2713"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.8.2836.420k35_2836_2843"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1099-1069(200009)18:3<87::AID-HON661>3.0.CO;2-8"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.154.3757.1662"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0903-679"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-0734.2000.00001.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2400713"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(06)70723-9"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.12.4990.bloodjournal87124990"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00256695"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2005.1.278"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2395"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.14.4.457"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02718"},{"key":"e_1_2_6_19_1","first-page":"1610","article-title":"Recent progress in chronic lymphocytic leukemia. 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