ABSTRACT
NK cells have unique attributes to react towards cells undergoing malignant transformation or viral infection. This reactivity is regulated by activating or inhibitory germline encoded receptors. An impaired NK cell function may result from an aberrant expression of such receptors, a condition often seen in patients with hematological cancers. Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer worldwide and NK cells have emerged as crucial targets for developing immunotherapies. However, there are important gaps concerning the phenotype and behavior of NK cells during emergence of ALL. In this study we analyze the phenotype and function of NK cells from peripheral blood in pediatric patients with ALL at diagnosis. Our results showed that NK cells exhibited an altered phenotype highlighted by a significant reduction in the overall expression and percent representation of activating receptors compared to age-matched controls. No significant differences were found for the expression of inhibitory receptors. Moreover, NK cells with a concurrent reduced expression in various activating receptors, was the dominant phenotype among patients. An alteration in the relative frequencies of NK cells expressing NKG2A and CD57 within the mature NK cell pool was also observed. In addition, NK cells from patients displayed a significant reduction in the ability to sustain antibody-dependent cellular cytotoxicity (ADCC). Finally, an aberrant expression of activating receptors is associated with the phenomenon of leukemia during childhood.
ABSTRACT
ETV6::RUNX1 is a genetic rearrangement of good prognosis in children with acute lymphoblastic leukemia (ALL). In Mexico, its prevalence is low in comparison with Caucasian populations. We developed a novel TaqMan one-step RT-qPCR approach to assess the prevalence of four genetic rearrangements in a cohort of Hispanic children with ALL from Mexico City. The prevalence of common fusion gene transcripts was as follows: TCF3::PBX1 7.7%; BCR::ABL1p 190 3.3%; and KMT2A::AFF1 2.8%, and ETV6::RUNX1was observed with low prevalence (10.5%) in comparison to that reported for developed countries. This is consistent with previous findings on Mexican children with ALL and similar to those reported on children from Hispanic populations. The confirmation of a low prevalence of ETV6::RUNX1 in children of a Hispanic origin represents an advancement in the description of genetic factors of ALL in these populations.
ABSTRACT
BACKGROUND: Refining risk stratification to avoid very early relapses (VER) in Mexican patients with B-lineage acute lymphoblastic leukemia (B-ALL) could lead to better survival rates in our population. AIM OF THE STUDY: The purpose of this study was to investigate the association between the United Kingdom ALL (UKALL)-CNA classifier and VER risk in Mexican patients with childhood B-ALL. METHODS: A nested case-control study of 25 cases with VER and 38 frequency-matched controls without relapse was conducted within the MIGICCL study cohort. They were grouped into the categories of the UKALL-CNA risk classifier (good [reference], intermediate and poor), according to the results obtained by multiplex ligation dependent probe amplification. Overall and disease-free survival (DFS) were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards analyses were conducted. RESULTS: The CDKN2A/B genes were most frequently deleted in the group with relapse. According to UKALL-CNA classifier, 33 (52.4%) patients were classified as good, 21 (33.3%) intermediate and 9 (14.3%) poor-risk B-ALL. The intermediate and poor risk groups were associated with an increased risk of VER (HR = 4.94, 95% CI = 1.87-13.07 and HR = 7.42, 95% CI = 2.37-23.26, respectively) in comparison to the good-risk patients. After adjusting by NCI risk classification and chemotherapy scheme in a multivariate model, the risks remained significant. CONCLUSIONS: Our data support the clinical utility of profiling CNAs to potentially refine current risk stratification strategies of patients with B-ALL.
