Characterization of Philadelphia-like Pre-B Acute Lymphoblastic Leukemia: Experiences in Mexican Pediatric Patients

• Published in: International journal of molecular sciences Vol. 23; no. 17; p. 9587
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2022; MDPI
• Subjects: Abnormalities; Acute lymphoblastic leukemia; Chemotherapy; children; Cloning; CRLF2 overexpression; Diagnostic systems; Flow cytometry; Gene expression; Genes; Genomics; Heavy chains; Immunoglobulins; Janus kinase 2; Kinases; Leukemia; Markers; Mexican; Mutation; Patients; pCrkl; Pediatrics; Ph-like; Phosphorylation; pre-B ALL; Proteins; Stat5 protein; Transcription factors; Mexico
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23179587

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.