Biomaterial Database

High occurrence of CRLF2 abnormalities in Mexican children with B-cell acute lymphoblastic leukemia. 2022

María Del Rocío Juárez-Velázquez, and Dafné Linda Moreno-Lorenzana, and Daniel Alejandro Martínez Anaya, and Eduardo Adrián Hernández Monterde, and María Montserrat Aguilar-Hernández, and Adriana Reyes-León, and María Antonieta Chávez-González, and Norma López Santiago, and Marta Zapata Tarrés, and Luis Juárez Villegas, and Netzi Rivera Sánchez, and Oscar Soto Lerma, and Lourdes Vega-Vega, and Roberto Rivera Luna, and Patricia Pérez-Vera

Laboratorio de Genética y Cáncer, Instituto Nacional de Pediatría, Mexico City, Mexico.

The P2RY8-CRLF2 and IGH-CRLF2 rearrangements induce the overexpression of cytokine receptor-like factor 2 (CRLF2) and have been associated with relapse and poor prognosis in B-cell acute lymphoblastic leukemia (B-ALL). Additionally, they are frequently documented in high-risk Hispanic populations. To better understand the potential causes of the adverse prognosis of childhood B-ALL in Mexico, we analyzed these rearrangements and the CRLF2 mRNA and protein levels in 133 Mexican children with B-ALL. We collected bone marrow samples at diagnosis and evaluated the CRLF2 gene expression by qRT-PCR and the total CRLF2 protein by flow cytometry. P2RY8-CRLF2 and IGH-CRLF2 were detected by RT-PCR and FISH, respectively. The median time of follow-up to determine the prognostic significance of the CRLF2 abnormalities was three years. In 82% of the participants, the mRNA levels correlated with the cell-surface and intracellular CRLF2 protein levels. The P2RY8-CRLF2 rearrangement was present in 31.5% (42/133) of the patients, while the IGH-CRLF2 rearrangement was detected in 13.5% (9/67) of patients with high expression of CRLF2 (6.8% of the total sample). CRLF2 copy number variations (gain) were also detected in 7.5% (5/67) of patients with high protein levels. The overall survival (OS) presented significantly lower rates in patients with high white blood cell count (≥50x109/L) regardless of CRLF2 expression, but high levels of CRLF2 gene expression appears to contribute to the reduction of OS within this group of patients. In conclusion, in our cohort, a high occurrence of CRLF2 abnormalities was documented, particularly the P2RY8-CRLF2 rearrangement, which might represent a characteristic of the Mexican population. Targeted therapy to treat this group of patients could improve OS.

UI	MeSH Term	Description	Entries
D008800	Mexico	A country in NORTH AMERICA, bordering the Caribbean Sea and the Gulf of Mexico, between BELIZE and the UNITED STATES, and bordering the North Pacific Ocean, between Guatemala and the UNITED STATES.
D011379	Prognosis	A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.	Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D015452	Precursor B-Cell Lymphoblastic Leukemia-Lymphoma	A leukemia/lymphoma found predominately in children and adolescents and characterized by a high number of lymphoblasts and solid tumor lesions. Frequent sites involve LYMPH NODES, skin, and bones. It most commonly presents as leukemia.	Leukemia, Pre-B-Cell,Pre-B-Cell Leukemia,Pre B-ALL,Pre-B ALL,Precursor B-Cell Lymphoblastic Leukemia,Precursor B-Cell Lymphoblastic Lymphoma,Leukemia, Pre B Cell,Leukemias, Pre-B-Cell,Pre B ALL,Pre B Cell Leukemia,Pre-B-Cell Leukemias,Precursor B Cell Lymphoblastic Leukemia,Precursor B Cell Lymphoblastic Leukemia Lymphoma,Precursor B Cell Lymphoblastic Lymphoma
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma	A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.	Leukemia, Lymphoblastic,Leukemia, Lymphoid, Acute,Lymphoblastic Leukemia,Lymphoblastic Lymphoma,Lymphocytic Leukemia, Acute,Lymphoma, Lymphoblastic,ALL, Childhood,Acute Lymphoid Leukemia,Leukemia, Acute Lymphoblastic,Leukemia, Lymphoblastic, Acute,Leukemia, Lymphoblastic, Acute, L1,Leukemia, Lymphoblastic, Acute, L2,Leukemia, Lymphoblastic, Acute, Philadelphia-Positive,Leukemia, Lymphocytic, Acute,Leukemia, Lymphocytic, Acute, L1,Leukemia, Lymphocytic, Acute, L2,Lymphoblastic Leukemia, Acute,Lymphoblastic Leukemia, Acute, Adult,Lymphoblastic Leukemia, Acute, Childhood,Lymphoblastic Leukemia, Acute, L1,Lymphoblastic Leukemia, Acute, L2,Lymphocytic Leukemia, L1,Lymphocytic Leukemia, L2,Acute Lymphoblastic Leukemia,Acute Lymphocytic Leukemia,Childhood ALL,L1 Lymphocytic Leukemia,L2 Lymphocytic Leukemia,Leukemia, Acute Lymphocytic,Leukemia, Acute Lymphoid,Leukemia, L1 Lymphocytic,Leukemia, L2 Lymphocytic,Lymphoid Leukemia, Acute,Precursor Cell Lymphoblastic Leukemia Lymphoma
D056915	DNA Copy Number Variations	Stretches of genomic DNA that exist in different multiples between individuals. Many copy number variations have been associated with susceptibility or resistance to disease.	Copy Number Polymorphism,DNA Copy Number Variant,Copy Number Changes, DNA,Copy Number Polymorphisms,Copy Number Variants, DNA,Copy Number Variation, DNA,DNA Copy Number Change,DNA Copy Number Changes,DNA Copy Number Polymorphism,DNA Copy Number Polymorphisms,DNA Copy Number Variants,DNA Copy Number Variation,Polymorphism, Copy Number,Polymorphisms, Copy Number
D018121	Receptors, Cytokine	Cell surface proteins that bind cytokines and trigger intracellular changes influencing the behavior of cells.	Cytokine Receptors,Cytokine Receptor,Receptors, Cytokines,Cytokines Receptors,Receptor, Cytokine