Jorge Vela Ojeda

CD133+CD34+ and CD133+CD38+ blood progenitor cells as predictors of platelet engraftment in patients undergoing autologous peripheral blood stem cell transplantation

BACKGROUND Hematopoietic stem cells (HSC) have been characterized by CD34+ expression and an adequate dose of CD34+ cells is associated with a complete engraftment. CD133 is a more specific marker of HSC. MATERIALS AND METHODS We studied the relationship between graft content of CD34+, CD133+, and CD38+ cells and trilineage engraftment after autologous stem cell transplantation in patients with different hematological disorders. Blood samples were obtained before and after mobilization with recombinant granulocyte-colony stimulating factor (G-CSF, 16 μg/kg), from apheresis collections, and after transplantation. RESULTS Cell subsets were quantified by flow cytometry, and the dose of each population infused was correlated with success of engraftment. G-CSF induced mobilization of CD133+CD38+ cells (12.6-fold) and CD133+CD34+ cells (14.7-fold). A correlation was observed between the infused dose of CD133+CD34+ and CD133+CD38+ cells and platelet engraftment. CONCLUSION CD133+CD34+ and CD133+CD38+ cells were mobilized with G-CSF and these cell subsets were correlated with platelet engraftment.

Genetic susceptibility variants for chronic lymphocytic leukaemia in Mexican mestizos

Chronic lymphocytic leukaemia (CLL) is the most common form of lymphoid neoplasia in countries with a predominant Caucasian population (Weiss, 1979). Nevertheless, it is very rare in Asia and Latin America, including Mexico (RuizArg€ uelles et al, 1999; Lan et al, 2010). The cause of the different incidences described for CLL between populations remains elusive. Six genetic susceptibility variants for CLL have been identified in genome-wide association studies (GWAS) carried out in Caucasians (Di Bernardo et al, 2008; CrowtherSwanepoel et al, 2010a,b). An attempt to replicate these results in Chinese patients found a significant association for three out of the six variants studied, with discrepancies in the frequencies of the risk alleles (Lan et al, 2010). The strongest associated loci for rs872071 on 6p25 3, encompassing the interferon regulatory factor gene (IRF4), lead to the development of a novel mouse model of CLL (Shukla et al, 2013). In order to explore whether the genetic susceptibility variants for CLL found in Caucasians and replicated in Asians may influence CLL risk in Mexican mestizos, we genotyped six single nucleotide polymorphisms (SNPs) in 117 CLL patients and 117 unrelated Mexican mestizo residents of Mexico City with normal lymphocyte counts. Controls were individually paired by sex and age in 5-year intervals. In order to be included in the study, all cases and controls were required to speak Spanish as their native language and to have Mexican heritage of at least three generations. Forty nine percent of patients were male. Median age at inclusion was 70 6 years (range 40 to 93 8 years), with a median age at CLL diagnosis of 67 years (range 38 6 to 92 7 years). The minor allele frequencies (MAFs) of all variants in Mexican mestizos were significantly different to frequencies described in the Chinese population. The MAFs for cases with rs13397985 and in all subjects with rs735665 were different from those described for Caucasians. Genotype distribution, odds ratio (OR) and 95% confidence interval (CI) for each of the six SNPs assuming a dominant model are shown in Table I. From the six polymorphisms studied, rs872071 was significantly associated with CLL (OR = 2 93; 95%CI = 1 47–5 82; P = 0 002). When a trend test was performed assuming an additive model, the association with rs872071 remained statistically significant (P = 0 012) (Table II). Finally, receiver-operator characteristic (ROC) analysis showed that the rs872071 genotype (AUC = 0 584, P = 0 027, 95%CI = 0 511–0 657) significantly predicted the diagnosis of CLL. The presence of the risk allele of rs872071 was not affected by the origin of the subjects and we did not find any interaction between ascendance and CLL risk. Although Asian and Latin-American countries share a low prevalence of CLL as compared with Caucasians (Groves et al, 1995), the clinical and molecular features of the disease are quite similar among all these populations (Boggs et al, 1987; Kawamata et al, 2013). Some probable explanations for the low prevalence of CLL in Asians and Mexicans may be either the contribution of different genetic risk alleles to the aetiology of this disease or the existence of protective factors in the genome of Asian ancestors conserved through migration and the admixture with different populations. Our results are in line with those of Di Bernardo et al (2008) and Lan et al (2010), finding rs872071 as the locus with the best association with CLL risk. These findings are supported by the decreased IRF4 expression in lymphocytes carrying the guanine allele of this variant (Di Bernardo et al, 2008), and the spontaneous development of CLL in Vh11 knock-in mice deficient in IRF4 (Shukla et al, 2013).