Hypoplastic form of myelodysplastic neoplasm.

BACKGROUND: Hypoplastic myelodysplastic neoplasm (MDS-h) is a rare hematopoietic disorder characterized by peripheral cytopenia, hypoplasia (cellularity ≤ 25%) and dysplastic changes in the bone marrow. Compared to normo- /hypercellular MDS, in addition to hypocellularity, MDS-h patients have more profound neutropenia and thrombocytopenia, a lower percentage of blasts, and less frequent abnormal karyotype. It is difficult to distinguish MDS-h from aplastic anemia in differential diagnosis. Abnormal karyotype is found in 15-50% of MDS-h patients and the most common chromosomal aberrations include -5/del (5q), -7/del (7q), +8, 17pLOH, del (20q), UPD at 4q, 11q, 13q, and 14q. Approximately 35% of MDS-h patients harbour somatic mutations that are most often detected in PIGA, TET2, DNMT3A, RUNX1, NPM1, ASXL1, STAG2, and APC genes. An autoimmune destruction of hematopoietic stem cells (HSCs) or hematopoietic progenitor cells (HPCs) mediated by abnormally activated T cells plays a key role in the pathophysiology of MDS-h. Expanded T cells overproduce proinflammatory cytokines (IFN- g and TNF-a), which inhibit proliferation and induce apoptosis of HSC/HPCs. The antigens that trigger the immune response are not known, but potential candidates have been suggested such as WT1 protein and HLA class I molecules. MDS-h does not represent a phenotypically homogeneous subtype of MDS, but rather it is a mixed entity comprising both patients showing features similar to myelodysplastic neoplasm and patients with features of non-malignant bone marrow failure. Determining the prevailing phenotype in MDS-h is important for choosing the optimal treatment and prognosis prediction. PURPOSE: The aim of this article is to point out an interesting hypoplastic MDS, the diagnosis of which is difficult, and to provide an overview of its main clinical-pathological features, genetic background, and mechanisms of aberrant immune response.

Plethysmographic and biochemical markers in the diagnosis of endothelial dysfunction in pediatric acute lymphoblastic leukemia survivors - new applications.

Acute lymphoblastic leukemia (ALL) and its treatment are associated with endothelial dysfunction (ED) and increased cardiovascular risk in adulthood. There are no data on ED in children after successful treatment of ALL. We aimed to assess new ED in these children using the plethysmographic reactive hyperemia index (RHI) and biomarkers that are known to be related to ED. In all, 22 children (mean 15.6 years), after successful treatment of ALL, and 18 healthy subjects were included in this prospective study. RHI, plasma concentrations of asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP) and E-selectin were measured in all children. RHI values were significantly lower in ALL patients when compared with healthy controls (p<0.05). hsCRP was significantly increased in ALL patients compared with the control group (p<0.001). E-selectin plasma levels were higher in ALL patients as compared to healthy controls (p=0.05). This is the first study that combines both plethysmographic and biochemical methods to assess ED in ALL survivors. Significantly decreased RHI with elevated plasma concentrations of biochemical markers imply a possible association with premature ED in ALL patients. The combined diagnostic approach seems to be a valuable tool for more accurate detection of ED and preventive cardiovascular management in these patients.