The effect of azacitidine therapy on the M protein of MDS patients with concomitant MGUS

Oka, Shiro; Ôno, Kazuo; Nohgawa, Masaharu

doi:10.1002/ajh.25160

Cited by 1 publication

(2 citation statements)

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“…MGUS is a precancerous condition characterized by an asymptomatic increase in plasma cells. MGUS is observed in 3.5% of individuals over 50 years of age [8,9]. Various pathophysiological conditions such as kidney failure, anemia, hypercalcemia, thrombocytopenia, lytic bone lesions, and bone pain occur because of the extra protein and monoclonal antibodies produced as a result of conversion from MGUS to MM, which complicates the patient's life [10].…”

Section: Discussionmentioning

confidence: 99%

“…The importance of TP53 in tumor suppression in malignancies is well established. TP53 dysregulation is involved in the pathogenesis of many malignancies [8]. On the other hand, the importance of other genes that regulate the cellular response to DNA damage and stress by being in the same pathway as p53 in MGUS MM transformation is not clear enough [3,5].…”

Section: Discussionmentioning

confidence: 99%

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MGUS'ta azalmış GADD45A gen ifadesi seviyesi

2023

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Purpose: Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia. It is known that MGUS has an increased risk of progression to multiple myeloma (MM), and also prepares the ground for diseases such as Waldenstrom macroglobulinemia (WM), non-Hodgkin lymphoma, and chronic lymphocytic leukemia (CLL). Our study aimed to evaluate whether some important p53 pathway genes differ in terms of expression in MGUS and healthy individuals. Materials and methods: For the study, bone marrow was collected from 8 healthy individuals and 8 individuals diagnosed with MGUS, and RNA samples were isolated. Expression levels of various genes involved in the p53 pathway were compared using the RT2-profiler PCR array. β-actin housekeeping gene expression level was used for normalization. The Pearson Correlation analysis and Receiver Operating Characteristic (ROC) analysis were conducted. Results: Among the genes whose expression levels were examined in this study, it was determined that the expression level of only the GADD45A gene decreased significantly in MGUS compared to the control group (p=0.027). Pearson correlation data showed that GADD45A gene expression was highly correlated with 12 of the other genes (APAF1, CDK4, PCNA, BAX, CDKN2A, CASP9, CHECK2, MDM2, RB1, P53, BCL2, CHEK1) examined in the p53 pathway (r>0.7). In addition, according to the ROC analysis, GADD45A is detected to have a strong discrimination power between MGUS and healthy individuals (AUC=0.797 and p=0.015). Conclusion: The decreased expression of the GADD45A gene in the MGUS group compared to the control group may be useful as a new biomarker to detect the risk of progression from MGUS to MM.

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Section: Discussionmentioning

confidence: 99%