SOLUBLE CXCR4, SURVIVIN, AND EXOSOMAL BCL-2: PROM ISING MARKERS FOR THE DIAGNOSIS OF LEUKEMIA AND EVALUATION THE INHIBITORY EFFICACY OF CHEMOTHER APY

Abstract

Background: Malignant tumors are associated with cancer term due to their lack of a protective capsule and their invasive and metastatic properties. Maliglishing secondary tumors in distant parts of the body through metastasis. Metastasis is a crucial feature distinguishing malignant tumors from benign ones. During metastasis, cancer cells spread from a  primary organ or tissue to a secondary site, promoting angiogenesis, the formation of new blood vessels. This  process supports the growth and development of tumors by supplying the nutrients and   oxygen necessary for their survival and expansion The term ‘’leukemia’’ is derived from an ancient Greek word  leukos (white) and haima (blood) that means ‘’white blood’’ therefore it refers to a wide range of malignant disorders in hematopoietic stem cells (HSCs) in the bone marrow due to the  accumulation of abnormal white blood cells (WBCs). The duration of this     disease varies depending on the type of leukemia, therapeutic methods and patients’ response. Thus, leukemia is considered one of the most aggressive, dangerous hematologic disorder types of cancers all over the world. The   current study aims to identify new prognostic markers for leukemias, distinguishing them from healthy individuals, and then monitor the effect of chemotherapy on suppressing carcinogenesis and achieving remission after receiving at least three consecutive    chemotherapy doses. The study design was implemented practically by assessing the levels of      Soluble C-X-C Motif Chemokine Receptor 4 "Soluble CXCR4", Survivin, and Exosomal BCL-2. Patients and Healthy Control: During 7 months, a total of 60 individuals were enrolled in the current study, they are divided into two main groups: Leukemic patients group, that  included 30 patients diagnosed with various types of leu kemia, they ranging in age from 16 to 79 years, and Healthy Controls that included 30 healthy individuals, they ranging in age from 12 to 70 years. The samples of patients with leukemia were collected from the National Oncology and He matology Hospital in Najaf Governorate, as well as Hematology and Oncology Hospital-Medical City of Al-Imam Al Hussain in Karbala Governorate before chemotherapy and were followed up during the chemotherapy period. This group included 4different types of leukemia ALL, AML, CLL and CML. All patients with different types of leukemia were diagnosed by oncologists. Sandwich  ELISA technique was applied to evaluate the studied criteria. Results: The results showed a significant increase in  soluble CXCR4 levels in the study patients before (p=0.000) and after receiving treatment together, as well as when comparing the study patients before receiving treatment with the control group. The study revealed significant  differences when comparing Survivin levels in the leukemia group before receiving chemotherapy compared to the same samples after completing chemotherapy (p=0.000), as well as their coun terparts in the control group (p=0.000).  ANOVA test revealed a significant increase in Exosomal BCL-2 levels in leuke mia patients before chemotherapy compared to healthy individuals (p=0.000), as well as compared to samples from the leukemia patient group after three consecutive doses of chemotherapy. The results of the correlation test between Soluble CXCR4 and both Survivin and Exosomal BCL-2; respectively, indicate statistically significant positive correlations in the group of patients with leukemia at diagnosis. On the other hand, the study showed a positively signigicant correlation only    between Soluble CXCR4 and Exosomal BCL-2 (r=0.648 at p=0.033) in the control group. Despite the significant decrease in the levels of Soluble CXCR4, Survivin and Exosomal BCL-2 to nearly the levels of the control group after receiving at least 3 consecutive doses of chemotherapy, the relationship between Soluble CXCR4 and both Survivin and Exosomal BCL-2 remained positive and statistically acceptable.a significant positive correlation between Survivin to Exosomal BCL-2 in approximately 91 individuals of the leukemia patient group before treatment, while no such results were recorded in the control group. With the same manar, the outcomes indicate that the relationship between Survivin and Exosomal BCL-2 remained significantly positive in the leukemia patient group after receiving chemotherapy,    de spite the decrease in the level of these two parameters to levels similar to those recorded in the group of healthy   individ uals. The individual  sensitivity and specificity of the evaluated criteria in the current study for diagnosting   cancerous patients reached the highest level (100%). Post-treatment, the results showed that the highest sensitivity (100%) were published for Survivin and Exosonal BCL-2, while the highest specificity (100%) was recorded for Survivin. Conclusions: The absolute sensitivity of the evaluated criteria provides them as three promising tools for  diagnosting different leukemic cases, and verifying the effectiveness of chemotherapy in treating leukemia.