Title:Altered Expression of MicroRNAs in the Bone Marrow of Multiple Myeloma Patients and their Relationship to Cytogenetic Aberrations
Volume: 21
Issue: 13
Author(s): Hanaa R.M. Attia*, Amany H. Abdelrahman, Mona H. Ibrahim, Maha M. Eid, Ola M. Eid, Mohamed T. Sallam, Mosaad M. El Gammal and Mahmoud M. Kamel
Affiliation:
- Department of Clinical and Chemical Pathology, National Research Centre, Cairo,Egypt
Keywords:
Multiple myeloma, cytogenetics, prognostic markers, microRNAs, B-cell malignancy, FISH.
Abstract:
Background: Multiple Myeloma (MM) is a complex hematologic malignancy, driven by
several genetic and epigenetic alterations. MiRNAs as biomarkers have become a rapidly growing research
area in the last decade.
Aim: The aim was to study the expression pattern of selected miRNAs and to explore the impact of cytogenetic
aberrations in MM patients for therapeutic tools.
Patients and Methods: Forty Egyptian adult patients were selected for the study with symptomatic
newly diagnosed MM disease. Bone marrow samples were collected to investigate twelve miRNAs selected
according to their relation to the most common cytogenetic aberrations with relevant prognostic
value. The relative expression of the selected miRNAs was determined using a real-time PCR technique.
Fluorescence In Situ Hybridization (FISH) technique was performed for cytogenetic analysis.
Results: Eight miRNAs were down-regulated [miR-15a (p<0.001), miR214-3p (p<0.001), miR135b
(p<0.001), miR19a-3p (p<0.001), miR19b-3p ((p=0.026), miR30e-5p (NS), miR133a (NS), miR146a-
5p (p<0.001)]. Four miRNAs were up-regulated [miR99b-5p (p=0.028), miR125a-3p (p=0.004), let7b-
5p (p<0.001), let7c-5p (p<0.001)]. Significant relation was observed between positive 14q32 rearrangement
using the break apart re-arrangement probe for 14q32.33 locus and lower expression levels
of miR15a (p= 0.014), 214-3p (p=0.046), 99b-5p (p=0.014), 146a-5p (p=0.041). A higher expression
level of miR30e-5p was significantly related to positive 14q32 rearrangement.
Conclusion: Deregulated miRNAs were identified and the association with 14q32 rearrangement and
MM pathogenesis has been determined.
