Proteomic Profiling Identifies Specific Leukemic Stem Cell-Associated Protein Expression Patterns in Pediatric AML Patients

Abstract

Novel therapeutic tools are warranted to improve outcomes for children with acute myeloid leukemia (AML). Differences in the proteome of leukemic blasts and stem cells (AML-SCs) in AML compared with normal hematopoietic stem cells (HSCs) may facilitate the identification of potential targets for future treatment strategies. In this explorative study, we used mass spectrometry to compare the proteome of AML-SCs and CLEC12A+ blasts from five pediatric AML patients with HSCs and hematopoietic progenitor cells from hematologically healthy, age-matched controls. A total of 456 shared proteins were identified in both leukemic and control samples. Varying protein expression profiles were observed in AML-SCs and leukemic blasts, none having any overall resemblance to healthy counterpart cell populations. Thirty-four proteins were differentially expressed between AML-SCs and HSCs, including the upregulation of HSPE1, SRSF1, and NUP210, and the enrichment of proteins suggestive of protein synthesis perturbations through the downregulation of EIF2 signaling was found. Among others, NUP210 and calreticulin were upregulated in CLEC12A+ blasts compared with HSCs. In conclusion, the observed differences in protein expression between pediatric patients with AML and pediatric controls, in particular when comparing stem cell subsets, encourages the extended exploration of leukemia and AML-SC-specific biomarkers of potential relevance in the development of future therapeutic options in pediatric AML.

Risk score constructed with neutrophil extracellular traps-related genes predicts prognosis and immune microenvironment in multiple myeloma

“…HSPE1 is a kind of heat shock protein. Studies have confirmed that HSPE1 is highly expressed in the leukemia stem cells of childhood AML (37), and other research indicated that upregulation of HSPE1 promoted…”

“…HSPE1 is a kind of heat shock protein. Studies have confirmed that HSPE1 is highly expressed in the leukemia stem cells of childhood AML ( 37 ), and other research indicated that upregulation of HSPE1 promoted prostate cancer progression ( 38 ). Our results showed that high expression of HSPE1 was detrimental to the prognosis of MM patients and was increased in MM patients compared to normal individuals.…”

A Comprehensive Metabolism-Related Gene Signature Predicts the Survival of Patients with Acute Myeloid Leukemia

“…ENO1 [27][28][29] and PC [31] were found to be overexpressed in several types of AML. A high expression of SDHA [41] and NUP210 [33,34] were positively associated with the unfavorable prognosis of AML patients and an elevated expression of SLC27A4 was linked to poorer clinical outcomes in several cancer types [35]. An upregulated level of SORT1 [37,38] and downregulated INSR [39] were both reported in chemo-resistant or relapsed AML samples.…”

Single-cell analysis of pediatric acute myeloid leukemia samples uncovers treatment-resistant stem and mast cells

“…Leukemic stem cells are considered a key driver of relapse in pAML 10,11 . Previous studies have identified potential LSC markers in cohorts of pAML from mixed cytogenetic backgrounds including CD69, CLEC12A, and gene sets such as the LSC6 and LSC17 11,12,61,62 . Our findings build on prior work by uncovering LSC markers from HRTR subtypes specific to RUNX1 and FLT3 pAML.…”