{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:42:06Z","timestamp":1785307326352,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Al-Ahliyya Amman University\/Jordan"},{"name":"Qatar National Library (QNL)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>(1) Background: Chronic myeloid leukemia is defined as the neoplastic development of mostly myeloid cells in the bone marrow. Several treatments, including chemotherapy, radiation, hormone treatment, and immunological therapy, can be used to control this condition. The therapeutic impact on leukemic individuals varies, and the response to therapy varies between patients due to disease heterogeneity. The primary goal of this study is to compare the effects of single and Imatinib (IM) and Hydroxyurea (HU) combined treatment on hematological parameters and gene expression in CML patients. (2) Methods: This study was conducted on 51 patients, with chronic myeloid leukemia, who were admitted to Al-Basher hospital in Amman, Jordan, for follow-up. Their hematological parameters were checked and gene expression was measured for (BCL2, PP2A, CIP2A, and WT1). (3) Results: The BCL2 gene was found to be less expressed in both IM and (HU + IM) treatments as compared to the HU group alone, while PP2A gene expression was raised. Such a thing indicates that the outcome of the combined therapy method is not ideal, since PP2A activation causes CML cells to move toward the blast crisis stage. Furthermore, CIP2A gene expression revealed that IM and (HU + IM) had the same therapeutic effect and were more successful in CML patients than HU alone. With regards to the treatment effect on hematological parameters, notably in CML patients in later stages, the combination therapy (HU + IM) raised lymphocyte count, indicating a greater response to the treatment. When compared to single medicines, the combination treatment reduced the proportion of neutrophils to normal reference ranges. Platelet counts, on the other hand, dramatically decreased in both IM and (HU + IM). (4) Conclusion: Because the studied genes (BCL2, PP2A, CIP2A, and WT1) are participating in cell proliferation and death, the findings show that the examined genes are significant to understand the efficacy of various therapies. Furthermore, it was found that there was a clear effect of the clinic-based strategic treatment on hematological indicators such as WBCs, lymphocytes, neutrophils, and platelet counts.<\/jats:p>","DOI":"10.3390\/jcm11174954","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:22:48Z","timestamp":1661300568000},"page":"4954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Investigation of the Effect of Imatinib and Hydroxyurea Combination Therapy on Hematological Parameters and Gene Expression in Chronic Myeloid Leukemia (CML) Patients"],"prefix":"10.3390","volume":"11","author":[{"given":"Esraa K.","family":"Al-Amleh","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan"},{"name":"Pharmacological and Diagnostic Research Center (PDRC), Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9361-9077","authenticated-orcid":false,"given":"Ola M.","family":"Al-Sanabra","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Science, Al-Balqa Applied University, Al-Salt 19117, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5819-0420","authenticated-orcid":false,"given":"Khalid M.","family":"Alqaisi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan"},{"name":"Pharmacological and Diagnostic Research Center (PDRC), Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moath","family":"Alqaraleh","sequence":"additional","affiliation":[{"name":"Pharmacological and Diagnostic Research Center (PDRC), Al-Ahliyya Amman University, Amman 19328, Jordan"},{"name":"Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jumana","family":"Al-Nahal","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Science, Al-Balqa Applied University, Al-Salt 19117, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4672-3303","authenticated-orcid":false,"given":"Lama","family":"Hamadneh","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6801-2126","authenticated-orcid":false,"given":"Mohammed Imad","family":"Malki","sequence":"additional","affiliation":[{"name":"College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0010-0381","authenticated-orcid":false,"given":"Jehad F.","family":"Alhmoud","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan"},{"name":"Pharmacological and Diagnostic Research Center (PDRC), Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nature07943","article-title":"The cancer genome","volume":"458","author":"Stratton","year":"2009","journal-title":"Nature"},{"key":"ref_3","unstructured":"Awad, A.A.A.R. (2022, July 01). Assessment of Complete Blood Count among Patients Receiving Chemotherapy at Tumor Therapy and Cancer Research Center in Shendi Town. Available online: http:\/\/localhost:8080\/xmlui\/handle\/123456789\/539."},{"key":"ref_4","unstructured":"Chennamadhavuni, A., Lyengar, V., and Shimanovsky, A. (2022, July 01). Leukemia. StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK560490\/."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1111\/bjh.14687","article-title":"Rodak\u2019s Hematology: Clinical Principles and Applications. By E.M. Keohane, L.J. Smith and J.M. Walenga (Eds), Elsevier, St Louis, 2016","volume":"177","author":"Bain","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_6","unstructured":"McKenzie, S.B., and Williams, J.L. (2015). Clinical Laboratory Hematology, Pearson PLC. [3rd ed.]."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-62703-002-1_7","article-title":"Application of reverse transcription-PCR and real-time PCR in nanotoxicity research","volume":"926","author":"Mo","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1182\/blood-2012-03-378919","article-title":"How I treat newly diagnosed chronic phase CML","volume":"120","author":"Cortes","year":"2012","journal-title":"Blood"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1080\/17512433.2018.1398644","article-title":"Pharmacology and pharmacokinetics of imatinib in pediatric patients","volume":"11","author":"Suttorp","year":"2018","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1007\/s00066-006-1445-8","article-title":"Human glioblastoma and carcinoma xenograft tumors treated by combined radiation and imatinib (Gleevec\u00ae)","volume":"182","author":"Oertel","year":"2006","journal-title":"Strahlenther. Und Onkol."},{"key":"ref_11","first-page":"19","article-title":"Simple spectrophotometric method for estimation of drugs using chloraminet and indigo caramine dye couple","volume":"10","author":"Delhi","year":"2020","journal-title":"Asian J. Biomed. Pharm. Sci."},{"key":"ref_12","first-page":"1","article-title":"Hydroxyurea-induced Amyopathic Dermatomyositis","volume":"3","author":"Amraoui","year":"2021","journal-title":"J. Clin. Med. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18","DOI":"10.22456\/2527-2616.100682","article-title":"Qualitative Analysis of Hydroxyurea","volume":"4","author":"Santos","year":"2020","journal-title":"Drug Anal. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s00280-009-0991-z","article-title":"Hydroxyurea and hydroxamic acid derivatives as antitumor drugs","volume":"64","author":"Saban","year":"2009","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Singh, A., and Xu, Y.J. (2016). The cell killing mechanisms of hydroxyurea. Genes, 7.","DOI":"10.3390\/genes7110099"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cell.2007.04.044","article-title":"CIP2A Inhibits PP2A in human malignancies","volume":"130","author":"Junttila","year":"2007","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"13944","DOI":"10.1073\/pnas.0506654102","article-title":"miR-15 and miR-16 induce apoptosis by targeting BCL2","volume":"102","author":"Cimmino","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1093\/jjco\/hyp194","article-title":"WT1 (Wilms\u2019 tumor gene 1): Biology and cancer immunotherapy","volume":"40","author":"Sugiyama","year":"2010","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"17013","DOI":"10.1038\/sigtrans.2017.13","article-title":"Overexpression of CIP2A is associated with poor prognosis in multiple myeloma. Cancerous inhibitor of protein phosphatase 2A (CIP2A), an endogenous protein phosphatase 2A (PP2A) inhibitor","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/nrc.2017.17","article-title":"Prospects for combining targeted and conventional cancer therapy with immunotherapy","volume":"17","author":"Gotwals","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/path.1706","article-title":"Molecular mechanisms of drug resistance","volume":"205","author":"Longley","year":"2005","journal-title":"J. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1475-2867-10-11","article-title":"From \u201comics\u201d to complex disease: A systems biology approach to gene-environment interactions in cancer","volume":"10","author":"Knox","year":"2010","journal-title":"Cancer Cell Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7753857","DOI":"10.1155\/2021\/7753857","article-title":"Mechanisms of Hydroxyurea-Induced Cellular Senescence: An oxidative stress connection?","volume":"2021","author":"Kapor","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1053\/j.seminhematol.2006.12.007","article-title":"The biology of chronic myelogenous leukemia: Implications for Imatinib therapy","volume":"44","author":"Alvarez","year":"2007","journal-title":"Semin. Hematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"355ra117","DOI":"10.1126\/scitranslmed.aag1180","article-title":"Combined targeting of BCL-2 and BCR-ABL tyrosine kinase eradicates chronic myeloid leukemia stem cells","volume":"8","author":"Carter","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"eaan8735","DOI":"10.1126\/scitranslmed.aan8735","article-title":"PP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL+ human leukemia","volume":"10","author":"Lai","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s12032-014-0112-7","article-title":"CIP2A is overexpressed and involved in the pathogenesis of chronic myelocytic leukemia by interacting with breakpoint cluster region-Abelson leukemia virus","volume":"31","author":"Wang","year":"2014","journal-title":"Med. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"38","DOI":"10.4103\/ejh.ejh_5_18","article-title":"Wilms\u2019 tumor gene 1 expression can predict sudden disease progression to blast crisis in patients with chronic myeloid leukemia receiving imatinib therapy","volume":"43","author":"Ahmed","year":"2018","journal-title":"Egypt. J. Haematol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1016\/j.leukres.2010.07.001","article-title":"\u201cReal-life\u201d results of front-line treatment with Imatinib in older patients (\u226565 years) with newly diagnosed chronic myelogenous leukemia","volume":"34","author":"Latagliata","year":"2010","journal-title":"Leuk. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Catellani, S., Pierri, I., Gobbi, M., Poggi, A., and Zocchi, M.R. (2011). Imatinib treatment induces CD5+ B Lymphocytes and IgM natural antibodies with anti-leukemic reactivity in patients with chronic myelogenous leukemia. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018925"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4864","DOI":"10.1182\/blood.V106.11.4864.4864","article-title":"Imatinib-related neutropenia in chronic-phase chronic myelogenous leukaemia: Safety and efficacy of granulocyte-colony-stimulating factor (Filgrastim) Use","volume":"106","author":"Lazzaro","year":"2005","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"127","DOI":"10.4274\/tjh.2014.0213","article-title":"Platelet dysfunction in patients with chronic myeloid leukemia: Does Imatinib mesylate improve it?","volume":"33","author":"Akay","year":"2016","journal-title":"Turk. J. Hematol."},{"key":"ref_33","first-page":"5473","article-title":"Higher red blood cell distribution width is an adverse prognostic factor in chronic-phase chronic myeloid leukemia patients treated with tyrosine kinase inhibitors","volume":"35","author":"Iriyama","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s10555-008-9119-x","article-title":"Protein phosphatase 2A (PP2A), a drugable tumor suppressor in Ph1(+) leukemias","volume":"27","author":"Perrotti","year":"2008","journal-title":"Cancer Metastasis Rev."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/17\/4954\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:14:17Z","timestamp":1760141657000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/17\/4954"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,24]]},"references-count":34,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["jcm11174954"],"URL":"https:\/\/doi.org\/10.3390\/jcm11174954","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,24]]}}}