Ph-like subtypes with CRLF2 abnormalities are frequent among Hispano–Latino children with pre-B ALL. Therefore, there is solid ground to suggest that this subtype is frequent in Mexican patients. The genomic complexity of Ph-like subtype constitutes a challenge for diagnosis, as it requires diverse genomic methodologies that are not widely available in diagnostic centers in Mexico. Here, we propose a diagnostic strategy for Ph-like ALL in accordance with our local capacity. Pre-B ALL patients without recurrent gene fusions (104) were classified using a gene-expression profile based on Ph-like signature genes analyzed by qRT-PCR. The expressions of the CRLF2 transcript and protein were determined by qRT-PCR and flow cytometry. The P2RY8::CRLF2, IGH::CRLF2, ABL1/2 rearrangements, and Ik6 isoform were screened using RT-PCR and FISH. Surrogate markers of Jak2-Stat5/Abl/Ras pathways were analyzed by phosphoflow. Mutations in relevant kinases/transcription factors genes in Ph-like were assessed by target-specific NGS. A total of 40 patients (38.5%) were classified as Ph-like; of these, 36 had abnormalities associated with Jak2-Stat5 and 4 had Abl. The rearrangements IGH::CRLF2,P2RY8::CRLF2, and iAMP21 were particularly frequent. We propose a strategy for the detection of Ph-like patients, by analyzing the overexpression/genetic lesions of CRLF2, the Abl phosphorylation of surrogate markers confirmed by gene rearrangements, and Sanger sequencing.

B-cell acute lymphoblastic leukemia is the most commonly diagnosed childhood malignancy worldwide; more than 50% of these cases are diagnosed in Mexico. Although the five-year survival rate is >80%, 30% of patients experience relapse with poor prognosis. Cancer-associated gene expression profiles have been identified in several malignancies, and some transcripts have been used to predict disease prognosis. The human transcriptome is incompletely elucidated; moreover, more than 80% of transcripts can be processed via alternative splicing (AS), which increases transcript and protein diversity. The human transcriptome is divided; coding RNA accounts for ~2%, and the remaining 98% is noncoding RNA. Noncoding RNA can undergo AS, promoting the diversity of noncoding transcripts. We designed specific primers to amplify previously reported alternative transcript variants of ZNF695 and showed that six ZNF695 transcript variants are co-expressed in cancer cell lines. The amplicons were sequenced and identified. Additionally, we analyzed the expression of these six transcript variants in bone marrow from B-cell acute lymphoblastic leukemia patients and observed that ZNF695 transcript variants one and three were the predominant variants expressed in leukemia. Moreover, our results showed the co-expression of coding and long noncoding RNA. Finally, we observed that long noncoding RNA ZNF695 expression predicted survival rates.

Background: B7H3 is a co-stimulatory molecule for immune reactions found on the surface of tumor cells in a wide variety of tumors. Preclinical and clinical studies have reported it as a tumor target towards which various immunotherapy modalities could be directed. So far, good results have been obtained in hematological neoplasms; however, a contrasting situation is evident in solid tumors, including those of the CNS, which show high refractoriness to current treatments. The appearance of cellular immunotherapies has transformed oncology due to the reinforcement of the immune response that is compromised in people with cancer. Objective: This article aims to review the literature to describe the advancement in knowledge on B7H3 as a target of CAR-T cells in pediatric gliomas to consider them as an alternative in the treatment of these patients. Results: Although B7H3 is considered a suitable candidate as a target agent for various immunotherapy techniques, there are still limitations in using CAR-T cells to achieve the desired success. Conclusion: Results obtained with CAR-T cells can be further improved by the suggested proposals; therefore, more clinical trials are needed to study this new therapy in children with gliomas.

Objective. To determine the magnitude of mortality due to acute lymphoblastic leukemia (ALL) nationally and by age group, sex, state of residence and insurance status, as well as to evaluate time trends during the period 1998-2018 Materials and methods. We obtained ALL mortality data and estimated age-standardized national, state-level and health insurance mortality rates. We conducted a joinpoint regression analysis to describe mortality trends across the study period and estimate the average annual percent change (AAPC). Results. In a 20-year period, age-standardized ALL mortality rates increased from 1.6 per 100 000 in 1998 to 1.7 in 2018. Nationally, a constant annual increase in mortality was observed for both sexes (1998-2002 AAPC 0.6 in boys, and 1998-2002 AAPC 0.3 in girls). We observed heteroge­neity in childhood ALL at a state level. Conclusion. Our results reflect the social, economic, geographic diversity of the country. Monitoring and surveillance of this disease is crucial to assess quality of care.