Clinical Monoclonal B Lymphocytosis versus Rai 0 Chronic Lymphocytic Leukemia: A Comparison of Cellular, Cytogenetic, Molecular, and Clinical Features
CLINICAL CANCER RESEARCH
Authors: Morabito, Fortunato; Mosca, Laura; Cutrona, Giovanna; Agnelli, Luca; Tuana, Giacomo; Ferracin, Manuela; Zagatti, Barbara; Lionetti, Marta; Fabris, Sonia; Maura, Francesco; Matis, Serena; Gentile, Massimo; Vigna, Ernesto; Colombo, Monica; Massucco, Carlotta; Recchia, Anna Grazia; Bossio, Sabrina; De Stefano, Laura; Ilariucci, Fiorella; Musolino, Caterina; Molica, Stefano; Di Raimondo, Francesco; Cortelezzi, Agostino; Tassone, Pierfrancesco; Negrini, Massimo; Monti, Sara; Rossi, Davide; Gaidano, Gianluca; Ferrarini, Manlio; Neri, Antonino
Purpose: To investigate the incidence and clinical relevance of classic and new prognostic markers, IGHV gene mutational status, and chromosomal abnormalities in clinical monoclonal B lymphocytosis (cMBL) compared with Rai stage 0 chronic lymphocytic leukemia (Rai0-CLL). Experimental Design: A group of 136 patients with cMBL and a group of 216 Rai0-CLL cases were investigated prospectively. Results: IGHV-mutated cases were significantly more frequent among cMBLs (P = 0.005), whereas the distribution of CD38 and ZAP-70 positive cases, of patients with NOTCH1 and SF3B1 mutations or exhibiting the major CLL cytogenetic abnormalities, was similar in the two groups. Moreover, no significant differences were found either in IGHV/IGHD/IGHJ gene usage or in the overall prevalence of stereotyped IGHV gene sequences. Cells from cMBL and Rai0-CLL exhibited similar gene and microRNA (miRNA) signatures; in addition, when grouped according to the IGHV mutational status, IGHV-unmutated cases showed different transcriptional signatures compared with IGHV-mutated patients, irrespective of the cMBL or Rai0-CLL classification. cMBL diagnosis per se was predictive of longer progression-free survival. Conclusions: Our study based on a prospective series of patients indicates that no major differences exist between the circulating cells from cMBL and Rai0-CLL, at least based on a comparison of the markers used in the study. This possibly suggests that the two conditions mainly differ in the initial size of the monoclonal cell population, which may influence the subsequent timing of clonal expansion and clinical manifestations. (C) 2013 AACR.
Hypothalamic abnormalities: Growth failure due to defects of the GHRH receptor
GROWTH HORMONE & IGF RESEARCH
Authors: Aguiar-Oliveira, Manuel H.; Davalos, Caridad; Tampos, Vivian C.; Oliveira Neto, Luiz A.; Marinho, Cindi G.; Oliveira, Carla R. P.
Several acquired or congenital hypothalamic abnormalities may cause growth failure (GF). We described two of these congenital abnormalities. First, a case of CHARGE syndrome, an epigenetic disorder mostly caused by heterozygous mutations in the gene encoding CHD7, a chromatin remodeling protein, causing several malformations, some life-threatening, with additional secondary hypothalamus-hypophyseal dysfunction, including GF. Second, a cohort of individuals with genetic isolated severe GH deficiency (IGHD), due to a homozygous mutation in the GH-releasing hormone (GHRH) receptor gene described in Itabaianinha County, in northeast Brazil. In this IGHD, with marked reduction of serum concentrations of IGF-I, and an up regulation of IGF-II, GF is the principal finding in otherwise normal subjects, with normal quality of life and longevity. This IGHD may unveil the effects of GHRH, pituitary GH and IGF-I, IGF-II and local GH and growth factor on the size and function of body and several systems. For instance, anterior pituitary hypoplasia, and impairment of the non-REM sleep may be due to GHRH resistance. Proportionate short stature, doll facies, high-pitched pre-pubertal voice, and reduced muscle mass reflect the lack of the synergistic effect of pituitary GH and IGF-I in bones and muscles. Central adiposity may be due to a direct effect of the lack of GH. Brain, eyes and immune system may also involve IGF-II and local GH or growth factors. A concept of physiological hierarchy controlling body size and function by each component of the GH system may be drawn from this model.