ABSTRACT
BACKGROUND: Acute myeloid leukemia (AML) results from sequential genetic alterations in a normal hematopoietic stem cell or its progenitors giving rise to an autonomous clone that dominates the bone marrow leading to marrow failure. MicroRNAs are short non-coding nucleic acid sequences that regulate post-transcriptional gene expression by base-pairing with their target mRNAs. MiRNAs can be secreted into extracellular fluids and carried to target cells by vesicles or bound to proteins. Intracellular and circulating miRNAs are believed to be useful markers in the diagnosis, prognosis, and treatment of various cancers. Practically, circulating miRNAs are more stable at room temperatures and extreme conditions. PURPOSE: This study aimed to compare the expression of miR-126-3p and miR-423-5p in patients and normal subjects and correlate their expression with response to induction therapy and with their 2-year overall survival rate. PATIENTS AND METHODS: Circulating miR-126-3p and miR-423-5p was measured in the plasma of 43 adult AML patients and 35 age- and sex-matched controls by quantitative reverse transcriptase PCR. The fold change in differential expression for each gene was calculated using the comparative cycle threshold method. RESULTS: There was an increase in the expression of the studied miRNAs in patients compared to the control group. The average expression fold change of miR-126-3p was 3.02 (p= 0.010). The average expression fold change of miR-423-5p was 4.09 (p= 0.003). No significant correlation was found between the expression of miR-126-3p and miR-423-5p in the studied AML patients (r = 0.094, p = 0.22). Furthermore, no relationship was found between the expression of the studied miRNAs and response to induction therapy or the 2-year survival rate. CONCLUSION: Although further studies are needed, our findings highlight the studied circulating miRNAs as possible diagnostic markers for AML.
ABSTRACT
BACKGROUND: Laboratory data suggest that acute myeloid leukemia AML originates from a rare population of cells, termed Leukemic Stem Cells (LSCs) or leukemia-initiating cells, which are capable of self-renewal, proliferation and differentiation into malignant blasts. There is a universal agreement that LSCs lie within the CD34+ compartment of hemopoietic cells and most of leukemic stem cells express the interleukin-3 alpha chain receptor, CD123 and lack CD38. This study aimed to estimate the expression of LSC phenotype in AML patients and to correlate it with response to induction therapy. METHODS: A cohort of 41 patients older than 15 years with newly diagnosed de novo AML were enrolled in this study. They were obtained from the National center of hematology in Baghdad and Baghdad teaching hospital between February and July 2013. The expression of CD34, CD38 and CD123 was assessed by multi-color flow cytometry. LSC positive (LSC+) samples must express CD34 and CD123 and lack the expression of CD38 in >1% of cells. French American British (FAB) classification system was used in this study. After four weeks of induction therapy; three groups were found: those who reached the Complete morphological Remission (CR), those who failed to reach CR and those who died before the assessment of morphological remission. The last two groups were merged for statistical purposes. RESULTS: After the course of induction therapy, 41.46% of patients had complete morphological remission while 58.54% of the studied patients failed to reach complete remission. The Complete Remission (CR) rate was higher (53.33%) in patients who were negative for LSC phenotype than patients who were positive for LSC phenotype (34.61%). CONCLUSION: LSCs were expressed in 63.41% of AML cases and were in approximate distribution in FAB M3 and non-M3 patients. The expression of LSC phenotype was associated with poor response to induction therapy in AML patients.
