The Expression of NTAL and Its Protein Interactors Is Associated With Clinical Outcomes in Acute Myeloid Leukemia

Author(s):Show less -

Thome, Carolina Hassibe ^{[1, 2, 3]} ; Ferreira, Germano Aguiar ^{[1, 2, 3]} ; Pereira-Martins, Diego Antonio ^{[2, 3, 4]} ; dos Santos, Guilherme Augusto ^{[2, 3]} ; Almeida-Silveira, Douglas R. ^{[5, 6]} ; Weinhauser, Isabel ^{[2, 3, 4]} ; de Souza, Gustavo Antonio ^[7] ; Houtsma, Roos ^[4] ; Schuringa, Jan Jacob ^[4] ; Rego, Eduardo M. ^{[2, 3, 6]} ; Faca, Vitor M. ^{[1, 2, 3]}

Affiliation

^[1] Univ Sao Paulo, Dept Biochem & Immunol, Ribeirao Preto Med Sch, Ribeirao Preto - Brazil

^[2] Univ Sao Paulo, Ctr Cell Based Therapy, Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Dept Internal Med, Ribeirao Preto Med Sch, Ribeirao Preto - Brazil

^[4] Univ Groningen, Univ Med Ctr Groningen, Canc Res Ctr Groningen, Dept Hematol, Groningen - Netherlands

^[5] AC Camargo Canc Ctr, Dept Hematol, Sao Paulo - Brazil

^[6] Univ Sao Paulo, LIM31, Hematol Div, Med Sch, Sao Paulo - Brazil

^[7] Oslo Univ Hosp, Dept Immunol, Rikshosp, Oslo - Norway

• Document type: Journal article
• Source: MOLECULAR & CELLULAR PROTEOMICS; v. 20, 2021.
• Web of Science Citations: 0

Abstract

Non-T cell activation linker (NTAL) membrane protein depletion from lipid rafts by alkylphospholipids or downregulation by shRNA knockdown decreases cell viability through regulation of the Akt/PI3K pathway in mantle cell lymphoma and acute promyelocytic leukemia cells. Here, we confirmed that the knockdown of NTAL in acute myeloid leukemia (AML) cell lines was associated with decreased cell proliferation and survival. Similarly, a xenograft model using AML cells transduced with NTAL-shRNA and transplanted into immunodeficient mice led to a 1.8-fold decrease in tumor burden. Using immunoprecipitation, LC-MS/MS analysis, and label-free protein quantification, we identified interactors of NTAL in two AML cell lines. By evaluating the gene expression signatures of the NTAL protein interactors using the PREdiction of Clinical Outcomes from Genomic Profiles database, we found that 12 NTAL interactors could predict overall survival in AML, in at least two independent cohorts. In addition, patients with AML exhibiting a high expression of NTAL and its interactors were associated with a leukemic granulocyte-macrophage progenitor-like state. Taken together, our data provide evidence that NTAL and its protein interactors are relevant to AML cell proliferation and survival and represent potential therapeutic targets for granulocyte-macrophage progenitor-like leukemias. (AU)

• FAPESP's process: 17/23117-1 - Evaluation of TP53/TP73 pathway in engraftment of acute promyelocytic leukemia cells in xenotransplantation model
• Grantee: Diego Antonio Pereira Martins
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/07675-3 - Study of PI3K/AKT signaling pathways in acute myeloid leukemia using selective ion monitoring (SRM).
• Grantee: Carolina Hassibe Thomé
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/09228-0 - Detection and functional analysis of Tumor-Associated Macrophages (TAM) in a transgenic model of acute promyelocytic leukemia (APL).
• Grantee: Isabel Weinhauser
• Support Opportunities: Scholarships in Brazil - Doctorate