Cell surface expression of GRP78 and CXCR4 is associated with childhood high-risk acute lymphoblastic leukemia at diagnostics

• Published in: Scientific reports Vol. 12; no. 1; p. 2322
• Main Authors: Angeles-Floriano, Tania, Rivera-Torruco, Guadalupe, García-Maldonado, Paulina, Juárez, Esmeralda, Gonzalez, Yolanda, Parra-Ortega, Israel, Vilchis-Ordoñez, Armando, Lopez-Martinez, Briceida, Arriaga-Pizano, Lourdes, Orozco-Ruíz, Dario, Torres-Nava, José Refugio, Licona-Limón, Paula, López-Sosa, Francisco, Bremer, Alhelí, Alvarez-Arellano, Lourdes, Valle-Rios, Ricardo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.02.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4028; 692/53; Acute lymphoblastic leukemia; Adolescent; Animals; Antigens, CD - metabolism; Blood; Bone marrow; Cancer; CD19 antigen; Cell Line; Cell surface; Child; Child, Preschool; Children; CXCR4 protein; Diagnosis; Endoplasmic reticulum; Endoplasmic Reticulum Chaperone BiP - metabolism; Female; Flow cytometry; Humanities and Social Sciences; Humans; Leukemia; Lymph nodes; Lymphatic leukemia; Male; Metastases; Mice; Mice, Inbred BALB C; multidisciplinary; Neoplasm Transplantation; Neoplastic Cells, Circulating - metabolism; Patients; Pediatrics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - etiology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Protein folding; Receptors, CXCR4 - metabolism; Risk Factors; Science; Science (multidisciplinary); Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-05857-w

Acute lymphocytic leukemia is the most common type of cancer in pediatric individuals. Glucose regulated protein (GRP78) is an endoplasmic reticulum chaperone that facilitates the folding and assembly of proteins and regulates the unfolded protein response pathway. GRP78 has a role in survival of cancer and metastasis and cell-surface associated GRP78 (sGRP78) is expressed on cancer cells but not in normal cells. Here, we explored the presence of sGRP78 in pediatric B-ALL at diagnosis and investigated the correlation with bona fide markers of leukemia. By using a combination of flow cytometry and high multidimensional analysis, we found a distinctive cluster containing high levels of sGRP78, CD10, CD19, and CXCR4 in bone marrow samples obtained from High-risk leukemia patients, which was absent in the compartment of Standard-risk leukemia. We confirmed that sGRP78 + CXCR4 + blood-derived cells were more frequent in High-risk leukemia patients. Finally, we analyzed the dissemination capacity of sGRP78 leukemia cells in a model of xenotransplantation. sGRP78 + cells emigrated to the bone marrow and lymph nodes, maintaining the expression of CXCR4. Testing the presence of sGRP78 and CXCR4 together with conventional markers may help to achieve a better categorization of High and Standard-risk pediatric leukemia at diagnosis.