High expression of Myosin 1g in pediatric acute lymphoblastic leukemia

Abstract

Acute Lymphoblastic Leukemia (ALL) is the most frequent cancer in pediatric population. Although the treatment has improved and almost 85% of the children are cured about 20% suffer relapse, therefore finding molecules that participate in the pathogenesis of the disease for the identification of relapse and patients at risk is an urgent unmet need. Class I myosins are molecular motors involved in membrane tension, endocytosis, phagocytosis and cell migration and recently they have been shown important for development and aggressiveness of diverse cancer types, however Myo1g an hematopoietic specific myosin has not been studied in cancer so far. We evaluated the expression of Myo1g by qRT-PCR, Immunocytochemistry and Immunofluorescence in a cohort of 133 ALL patients and correlated the expression at diagnosis and after treatment with clinical features and treatment outcomes. We found high expression levels of Myo1g in Peripheral Blood Mononuclear Cells (PBMCs) from patients with ALL at diagnosis and those levels decreased after complete remission; furthermore, we found an increase in Myo1g expression on patients with 9:22 translocation and those who relapse. This study show that Myo1g is over expressed in ALL and that may participate in the pathogenesis of the disease specially in high-risk patients.

Detection of Myosin 1g Overexpression in Pediatric Leukemia by Novel Monoclonal Antibodies

“…Myosin 1g is highly expressed in B and T lymphocytes; recently we demonstrated its overexpression in high-risk pediatric ALL patients [ 8 , 18 , 23 ]. In this study, we generated monoclonal antibodies against human Myo1g, and demonstrated that the three of them could recognize the endogenous protein in normal and transformed B and T cells, and evaluated their potential use in recognizing the overexpression of Myo1g in blood samples from pediatric ALL patients as a putative biomarker.…”

“…Myo1g participates in different cell functions, particularly regulating membrane tension and Fc receptor-mediated phagocytosis, controlling cell migration and the turning angles of T and B cells, especially under antigen-limited conditions [ 13 , 14 , 16 , 26 ]. Additionally, we demonstrated that Myo1g could be used as a high-risk biomarker in pediatric ALL [ 18 ]. Leukemia treatment has improved in recent years; however, 15–20% of patients relapse [ 27 , 28 ].…”

“…PBMCs from control individuals and ALL patients were adhered to glass slides as reported in [ 18 ]. Briefly, 50 µL spots with 10,000 PBMCs were left to dry, the cells were fixed with 50 µL of 4% paraformaldehyde (PFA) ( v / v ) and stored until use.…”

“…It also regulates lipid raft movement, spreading, migration, and antigen presentation in B lymphocytes [ 4 , 13 , 14 , 15 , 16 , 17 ]. Recently, we found that Myo1g is upregulated in patients with ALL [ 18 ]. Myo1g has not previously been directly linked to cancer; although, other Class I myosins have gained interest in the field because some function as tumor suppressors, while others are overexpressed in different cancers [ 19 , 20 , 21 ].…”

Cell-free DNA methylation profiles enable early detection of colorectal and gastric cancer

“…Notably, ATXN1 was found to be a component of Notch signaling pathway which is essential for the development and homeostasis of gastrointestinal epithelial cells [25,26]. Likewise, MYO1G as an essential regulator of membrane intension in T cells has been found involved in the lymphoblastic leukemia, and the class I myosins have been shown to be important for development and metastasis of diverse cancer types, including colorectal cancer [27,28]. Additionally, GNDF was reported to increase cell motility in colon cancer through Am J Cancer Res 2024;14(2):744-761…”