Differential expression of ribosomal proteins in myelodysplastic syndromes.

Aberrations of ribosomal biogenesis have been implicated in several congenital bone marrow failure syndromes, such as Diamond-Blackfan anaemia, Shwachman-Diamond syndrome and Dyskeratosis Congenita. Recent studies have identified haploinsufficiency of RPS14 in the acquired bone marrow disease isolated 5q minus syndrome, a subtype of myelodysplastic syndromes (MDS). However, the expression of various proteins comprising the ribosomal subunits and other proteins enzymatically involved in the synthesis of the ribosome has not been explored in non-5q minus MDS. Furthermore, differences in the effects of these expression alterations among myeloid, erythroid and megakaryocyte lineages have not been well elucidated. We examined the expression of several proteins related to ribosomal biogenesis in bone marrow biopsy specimens from patients with MDS (5q minus patients excluded) and controls with no known myeloid disease. Specifically, we found that there is overexpression of RPS24, DKC1 and SBDS in MDS. This overexpression is in contrast to the haploinsufficiency identified in the congenital bone marrow failure syndromes and in acquired 5q minus MDS. Potential mechanisms for these differences and aetiology for these findings in MDS are discussed.

Diagnostic microRNAs in myelodysplastic syndrome.

OBJECTIVE: The myelodysplastic syndromes (MDS) are aging-associated disorders characterized by ineffective maturation of hematopoietic elements, which are often diagnostically challenging. This study identifies microRNAs (miRNA) and miRNA targets that might represent diagnostic markers for MDS. MATERIALS AND METHODS: This study utilized a total of 42 MDS samples and 45 controls. A discovery set of 20 frozen bone marrow mononuclear cell samples (10 MDS, 10 controls) was profiled on a custom Agilent miRNA microarray. Classifier miRNAs were validated in a separate set of 49 paraffin-embedded particle preparations by real-time polymerase chain reaction (24 MDS, 25 controls). Target prediction analysis was compared to a de novo transcriptional profile of MDS derived from the Microarray Innovations in Leukemia study. c-Myb and Sufu were further investigated by immunohistochemical stains on a set of 26 paraffin-embedded samples. RESULTS: We identified 13 miRNAs of interest from the discovery set, 8 of which proved statistically significant on real-time polymerase chain reaction verification. These eight miRNAs were then examined in an independent real-time polymerase chain reaction validation set. Notably, hsa-miR-378, hsa-miR-632, and hsa-miR-636 demonstrated particularly high discrimination between MDS and normal controls. Target prediction identified potential targets of miRNA regulation that correspond to many of the genes that characterize MDS. Immunohistochemical staining performed on a third validation set confirmed that c-Myb and Sufu are differentially expressed in MDS. CONCLUSIONS: Our data utilize both discovery and validation sets and two complementary platforms to identify miRNAs associated with MDS. We have analyzed predicted targets and identified c-Myb and Sufu as potential diagnostic markers of MDS.

High Prevalence of Obesity in Acute Promyelocytic Leukemia (APL): Implications for Differentiating Agents in APL and Metabolic Syndrome.

BACKGROUND: Between January 1999 and December 2008, 469 patients treated for acute myeloid leukemia (AML) were included in this single-institution study. METHODS: We performed a case-control analysis to study the rate of obesity among patients with acute promyelocytic leukemia (APL) and non-APL AML. RESULTS: A total of 81% of APL patients analyzed were obese compared with 41.7% in the non-APL group (p < 0.001). Body mass index (BMI) >30 was seen in 57% of APL patients compared with 31% for the non-APL group (p = 0.01). Neither obesity nor the chemotherapy dosing based on ideal body weight affected survival. CONCLUSIONS: Our findings generate the hypothesis that APL and metabolic syndromes may share a common pathogenic pathway via retinoic acid receptors (RARs), the ligand-controlled transcription factors that function as heterodimers with retinoid X receptors (RXRs) to regulate cell growth and survival. If this link is confirmed in larger studies, our data will instigate further studies using RXR and RAR modulators as a preventive strategy among obese individuals.

Renal peripheral neuroectodermal tumor presenting at age 78: case report.

Primitive neuroectodermal tumor (PNET) of the kidney is a rare and aggressive tumor, often presenting in advanced stages and progressing rapidly. Renal PNET (rPNET) may affect a wide age spectrum, but the majority of cases are in young adults. We present a case of advanced rPNET in a 78-year-old woman. To our knowledge, this is the most advanced age of presentation of this neoplasm to date. We report on her presentation and management, and discuss the current clinical management of this tumor.