ABSTRACT
BACKGROUND: The lack of effectiveness of acute myeloid leukemia (AML) treatment remains a major challenge and resembles a principal cause of AML-related mortality owing to chemotherapy resistance. SNAI1 has been proved to be a leading factor in drug resistance in many cancer types. However, its relation to chemoresistance in AML is not well understood. METHODS: In addition to standard lab work, the expression level of SNAI1 was determined in bone marrow samples of 109 adult and pediatric patients with de novo acute myeloid leukemia using RT-qPCR. The relation between SNAI1 and AML drug resistance and immunomodulatory genes was investigated using the STRING tool. RESULTS: The SNAI1 expression level was upregulated in AML patients in particular samples with promyelocytic leukemia subtype against control cases. In the treatment response, SNAI1 was significantly higher in resistant patients in comparison with the complete remission group. SNAI1 overexpression was associated with high initial blasts and total leukocyte counts, but with HLA class II histocompatibility antigen DR downregulation. STRING analysis showed that multiple drug resistance and immunomodulatory genes of AML induce SNAI upregulation and activation. Kaplan-Meier analysis indicated that there was no relation between SNAI1 expression level and patient survival status. CONCLUSION: We conclude that the SNAI1 expression level may be a predictor of intrinsic drug resistance incidence in AML patients.
Subject(s)
Leukemia, Myeloid, Acute , Leukemia, Promyelocytic, Acute , Adult , Humans , Child , Bone Marrow , Acute Disease , Leukemia, Myeloid, Acute/genetics , Leukemia, Promyelocytic, Acute/drug therapy , HLA-DR Antigens/analysis , HLA-DR Antigens/therapeutic use , Drug Resistance , Snail Family Transcription FactorsABSTRACT
Epigenetics factors are critical for normal cell function and their regulation is sensitive to malignancy development. EHMT2/G9a and KDM2b are key epigenetics players in different cancer types. However, their expression profiles and related consequences in acute myeloid leukemia (AML) patients have not been known yet. In addition to routine lab work, expression levels of EHMT2/G9a and KDM2b were determined in 110 adult and pediatric patients with De Novo AML. Relations between their expression and patients' clinical data were tested by statistical methods. EHMT2/G9a and KDM2b were highly expressed in AML patients against control cases and associated with the presence of adverse genomic alterations. In response to induction chemotherapy, EHMT2/G9a and KDM2b showed to be significantly high in resistant and relapsed patients in comparison to the complete remission group. KDM2b overexpression was associated with CD11c (integrin alpha X) downregulation. Kaplan-Meier analysis indicated that EHMT2/G9a and KDM2b overexpression was correlated with poor survival status in AML patients. We conclude that EHMT2/G9a and KDM2b expression levels could be used as independent prognostic factors for AML disease.
Subject(s)
Chromatin , Leukemia, Myeloid, Acute , Adult , Child , Epigenesis, Genetic , Histocompatibility Antigens/genetics , Histone-Lysine N-Methyltransferase/genetics , Histone-Lysine N-Methyltransferase/metabolism , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , PrognosisABSTRACT
BACKGROUND: Genomic abnormalities were established as prognostic and diagnostic markers for acute myeloid leukemia (AML) tumorgenesis and YBX1 gene has important roles in different cancer types. METHODS: A total of 109 adult and pediatric patients with De novo AML, were enrolled in this study. Besides the routine lab work; bone marrow YBX1 expression levels were measured using qRT-PCR, and then its possible connections to AML pathogenesis pathway were investigated by STRING tool. RESULTS: Results demonstrated upregulation of YBX1 expression level in AML patients that was associated with the presence of adverse genomics abnormalities. In adult patients, the level of YBX1 expression was significantly high in relapsed and resistant groups, while in pediatric patients, the level of YBX1 expression showed an inverse pattern as it was highly expressed in complete remission group. STRING analysis highlighted that YBX1 interacts with important factors in the AML signaling pathway. Kaplan-Meier analysis indicated that adult patients with highly expressed YBX1 significantly endured shorter disease-free survival (DFS) compared to low YBX1 expressers and there was no impact of YBX1 on adult patients overall survival (OS). While pediatric patients with upregulated YBX1 showed good OS over downregulated patients. CONCLUSION: In conclusion, YBX1 may have a crucial role in AML relapse pathogenesis. Also, it could serve as a prognostic factor for AML disease outcomes.
