Investigation of the Effect of Imatinib and Hydroxyurea Combination Therapy on Hematological Parameters and Gene Expression in Chronic Myeloid Leukemia (CML) Patients

Esraa K Al-Amleh; Ola M Al-Sanabra; Khalid M Alqaisi; Moath Alqaraleh; Jumana Al-Nahal; Lama Hamadneh; Mohammed Imad Malki; Jehad F Alhmoud

doi:10.3390/jcm11174954

Investigation of the Effect of Imatinib and Hydroxyurea Combination Therapy on Hematological Parameters and Gene Expression in Chronic Myeloid Leukemia (CML) Patients

J Clin Med. 2022 Aug 24;11(17):4954. doi: 10.3390/jcm11174954.

Authors

Esraa K Al-Amleh^{1

2}, Ola M Al-Sanabra³, Khalid M Alqaisi^{1

2}, Moath Alqaraleh^{2

4}, Jumana Al-Nahal³, Lama Hamadneh⁵, Mohammed Imad Malki⁶, Jehad F Alhmoud^{1

2}

Affiliations

¹ Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan.
² Pharmacological and Diagnostic Research Center (PDRC), Al-Ahliyya Amman University, Amman 19328, Jordan.
³ Department of Medical Laboratory Sciences, Faculty of Science, Al-Balqa Applied University, Al-Salt 19117, Jordan.
⁴ Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan.
⁵ Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan.
⁶ College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar.

Abstract

(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.

Keywords: BCL2; CIP2A; CML; PP2A; WT1; gene expression; hydroxyurea; imatinib; leukemia.

Grants and funding

Financial support was offered by Al-Ahliyya Amman University/Jordan. Open Access funding provided by the Qatar National Library (QNL).