Apoptosis-Related Gene Expression Profiling in Hematopoietic Cell Fractions of MDS Patients

Contains fulltext : 168172.pdf (publisher's version ) (Open Access)Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially elucidated which genes are involved in this process and which hematopoietic cells are mainly affected. We employed sensitive real-time PCR technology to study 93 apoptosis-related genes and gene families in sorted immature CD34+ and the differentiating erythroid (CD71+) and monomyeloid (CD13/33+) bone marrow cells. Unsupervised cluster analysis of the expression signature readily distinguished the different cellular bone marrow fractions (CD34+, CD71+ and CD13/33+) from each other, but did not discriminate patients from healthy controls. When individual genes were regarded, several were found to be differentially expressed between patients and controls. Particularly, strong over-expression of BIK (BCL2-interacting killer) was observed in erythroid progenitor cells of low- and high-risk MDS patients (both p = 0.001) and TNFRSF4 (tumor necrosis factor receptor superfamily 4) was down-regulated in immature hematopoietic cells (p = 0.0023) of low-risk MDS patients compared to healthy bone marrow

Participación del miR-137 en el cáncer

MicroRNAs are small RNAs (18-100 nucleotides), which regulate the expression of their target genes at the post-transcriptional level; however, miRNAs have been detected at the nuclear level. MicroRNA hsa-mirR-137 is located within its host gene MIR137HG, in the locus 1p21.3, and regulates genes involved in cell proliferation and cell differentiation. This microRNA participates on the neurogenesis by suppressing the proliferation of neural stem cells and by promoting their differentiation. Because of these crucial functions, its participation has been focussed on the study of different neurological diseases and in cancer, where it functions as tumoral suppressor (nervous system tumors, melanoma, gastric and lung cancer, oral carcinoma, osteosarcoma, ovarian and breast cancer) or oncogene (bladder and breast cancer). According to these studies, miR-137 could function as a biomarker for diagnosis and prognosis, and as therapeutic target in many types of cancer; however, more studies are needed to establish these

Supplementary Material for: Duplication of the Miller-Dieker Critical Region in a Patient with a Subtelomeric Unbalanced Translocation t(10;17)(p15.3;p13.3)

Submicroscopic duplications in the Miller-Dieker critical region have been recently described as new genomic disorders. To date, only a few cases have been reported with overlapping 17p13.3 duplications in this region. Also, small deletions that affect chromosome region 10p14→pter are rarely described in the literature. In this study, we describe, to our knowledge for the first time, a 5-year-old female patient with intellectual disability who has an unbalanced 10;17 translocation inherited from the father. The girl was diagnosed by subtelomeric FISH and array-CGH, showing a 4.43-Mb heterozygous deletion on chromosome 10p that involved 14 genes and a 3.22-Mb single-copy gain on chromosome 17p, which includes the critical region of the Miller-Dieker syndrome and 61 genes. The patient’s karyotype was established as 46,XX.arr 10p15.3p15.1(138,206–4,574,436)x1,17p13.3(87,009–3,312,600)x3. Because our patient exhibits a combination of 2 imbalances, she has phenotypic features of both chromosome abnormalities, which have been reported separately. Interestingly, the majority of patients who carry the deletion 10p have visual and auditory deficiencies that are attributed to loss of the <i>GATA3</i> gene. However, our patient also presents severe hearing and visual problems even though <i>GATA3</i> is present, suggesting the involvement of different genes that affect the development of the visual and auditory systems

Supplementary Material for: Clinical and Molecular Characterization of a Patient with 15q21.2q22.2 Deletion Syndrome

We report on a 16-year-old girl with a complex phenotype, including intellectual disability, facial dysmorphisms, and obesity. During her infancy, she presented with weak sucking, global developmental delay, and later with excessive eating with central obesity. The girl was clinically diagnosed with probable Prader-Willi syndrome. Chromosomal analysis showed a de novo deletion 46,XX,del(15)(q21q22). However, the use of the Affymetrix CytoScan HD Array defined the exact breakpoints of the deleted 15q21q22 region. The imbalance, about 10.5 Mb in size, is to date the second largest deletion ever described in this chromosomal region. In addition, our patient carries a microdeletion in the 1q44 region and a gain in 9p24. The array result was arr[hg19] 9p24.1(6,619,823-6,749,335)×3, 1q44(248,688,586-248,795,277)×1, 15q21.2 q22.2(50,848,301-61,298,006)×1. Although our patient presents additional chromosomal alterations, we provide a correlation between the clinical findings and the phenotype of the 15q21 deletion syndrome