학술논문
Characterization of Philadelphia-like Pre-B Acute Lymphoblastic Leukemia: Experiences in Mexican Pediatric Patients.
Document Type
Article
Author
Martínez-Anaya, Daniel; Moreno-Lorenzana, Dafné; Reyes-León, Adriana; Juárez-Figueroa, Ulises; Dean, Michael; Aguilar-Hernández, María Montserrat; Rivera-Sánchez, Netzi; García-Islas, Jessica; Vieyra-Fuentes, Victoria; Zapata-Tarrés, Marta; Juárez-Villegas, Luis; Paredes-Aguilera, Rogelio; Vega-Vega, Lourdes; Rivera-Luna, Roberto; Juárez-Velázquez, María del Rocío; Pérez-Vera, Patricia
Source
Subject
*LYMPHOBLASTIC leukemia
*MEXICANS
*ACUTE leukemia
*GENE rearrangement
*BIOMARKERS
*CHILD patients
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Language
ISSN
1661-6596
Abstract
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. [ABSTRACT FROM AUTHOR]