Assessment of GM-CSF Level in the Serum of Patients with Different Stages of Chronic Myeloid Leukemia Befor and After Imatinb Mesylate Therapy

Abstract

Background: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of primitivehaemopoietic progenitor cells. The cytogenetic hallmark of CML is the Philadelphiachromosome, created by a reciprocal translocation between chromosomes 9&22 (t[9;22][q34;q11]). Survival and amplification of hematopoietic progenitors are controlled by anumber of regulatory molecules (hematopoietic growth factors). The role of Granulocytemacrophagecolony-stimulating factor (GM-CSF) and its receptor in pathology arises largely asa result of abnormal signaling leading to deregulated myelopoiesis. The development of theBCR-ABL-targeted Imatinib mesylate represents a paradigm shift in the treatment of CML.Data indicate that the level of immune responses against CML is low before Imatinib, rises astreatment is administered and declines again when the BCR-ABL transcript numbers fall to lowlevels.Objective: To assess and evaluate the significance of levels difference in GM-CSF through newlydiagnosed patients, different responder groups (optimal, suboptimal and failure cytogeneticresponse) and advanced stages (acceleration and crisis groups) of CML Iraqi patients whomreceiving Imatinib mesylate (TKI), as an indicator to assess the role of growth factor inpathogenesis of CML disease development and response to treatments.Patients and methods: In this study 128 Iraqi CML patients asses before and after receiving imatinibmesylate treatment which categorized by complete blood picture and fluorescent in situhybridization (FISH) analysis in to different response groups and stages, then used an ELISAtechnique to assess serum level of GM-CSF in each response group and advance stage(acceleration and transformed) of CML patients, in comparison to level in 32 healthy controlsubjects.Results: Out of 128 patients the mean of GM-CSF serum level (pg/ml) for the newly diagnosed,optimal responded, suboptimal responded, failure cytogenetic and advance stage of CML were399.53±104.50, 325.23±66.37, 428.90±45.70, 347.12±54.45, 521.56±83.73, respectively. Whilehealthy was 269.25±86.27.Conclusion: Uncontrolled granulopoiesis in newly diagnosed patients with CML may be mediated byincreased plasma CSF concentrations caused by BCR-ABL activity which may give an idearegarding the role of colony stimulating factors in the pathogenesis of CML disease.