Francisca
Lamini
EBF3 Modifies the Leukemic State in Acute Promyelocytic Leukemia
Abstract profile. Full document pending author claim.
Authors:
Francisca Lamini, Jonathan Lee, Frank Slack
Date Created:
2025-01-01
Course Title:
Professor:
Not specified
About Paper:
Acute Promyelocytic Leukemia (APL) is a special subtype of transcription. To validate our bioinformatic results, we performed Acute Myeloid Leukemia (AML) that is characterized by the reverse transcription quantitative polymerase chain reaction (RT- formation of the Promyelocytic Leukemia-Retinoic Acid Receptor qPCR) using NB4 cells. One group of NB4 cells was treated with Alpha (PML-RARA) fusion protein. While most APL patients all-trans retinoic acid (ATRA) dissolved in dimethyl sulphoxide harbor the treatment-sensitive PML-RARA fusion protein, a (DMSO), while a control group was treated with DMSO only. subset of APL patients exhibit non-PML-RARA fusions which EBF3 expression was significantly decreased (p ▯ 0.01) in the are resistant to treatment. Recent bioinformatic and functional ATRA-treated cells compared to the control. This observation is analyses from my lab (Slack Lab) have identified EBF3 (Early B- expected because ATRA exerts its therapeutic effect through many Cell factor 3) as a gene whose transcription levels are significantmechanisms, including the degradation of PML-RARA. Since our elevated in patients with PML-RARA status. Given these data, we preliminary data suggest that PML-RARA may transcriptionally hypothesize that EBF3 contributes to the leukemic state in both upregulateEBF3,itsdegradationshouldleadtoadecreaseinEBF3 PML-RARA and non-PML-RARA APL by acting as an oncogene. expression. Thus, modulating EBF3 activity may serve as a new To investigate this further, our goal is to use cell-based assays ttherapeutictargetfortreatment-resistantAPLpatientsandimprove determine how EBF3 gene regulation contributes to the leukemic their treatment outcomes and survival rates. state in APL. We will also test the roles of PML-RARA on EBF3 106 Program for Research in Science and Engineering SuppressorAnalysisofConditionalMutantsfortheEssentialChaperoneCtr86 in Saccharomyces cerevisiae William Le, Marina Barba, Vlad Denic Churchill College, University of Cambridge | Molecular and Cellular Biology | 2026 Spinocerebellar ataxia type 10 (SCA10) is a neurodegenerative Cas9 based treatment. The purpose of this research is therefore disease affecting coordination associated with a pentanucleotide to screen for mutants in Saccharomyces cerevisiae that can (ATTCT) repeat expansion in the ATXN10 gene. Whilst bypass the essentiality of Ctr86 using two conditional yeast the specific function of ATXN10 (homologous to Ctr86 in mutant strains. Strategies for mutagenesis involve spontaneous Saccharomyces cerevisiae) is unknown, AlphaPulldown predicts suppressor accumulation, UV mutagenesis, and RLI1 plasmid a highly confident interaction between human ATXN10 and non- library production via error prone PCR. This is followed by native ABCE1 (homologous to Rli1 in Saccharomyces cerevisiae), validation steps such as replica plating, PCR, and protein suggesting ATXN10 may be involved in the folding of ABCE1. expression analysis. Compensatory mutations in the RLI1 locus, ABCE1/Rli1 is a highly conserved essential gene in eukaryotes the only known Ctr86 client, are currently being screened followed which facilitates ribosome dissociation following translational by whole genome sequencing to identify suppressor mutations at termination. Characterizing the activity of ATXN10/Ctr86 other loci. From this screen, we hope to identify key residues or as a chaperone of ABCE1/Rli1 is therefore important to domains in Rli1/Ctr86 required for folding of Rli1 as well as other characterizing the pathogenic mechanism of SCA10 and the potential interaction partners of Ctr86. development of future therapeutic treatments, such as CRISPR-
Abstract:
Acute Promyelocytic Leukemia (APL) is a special subtype of transcription. To validate our bioinformatic results, we performed Acute Myeloid Leukemia (AML) that is characterized by the reverse transcription quantitative polymerase chain reaction (RT- formation of the Promyelocytic Leukemia-Retinoic Acid Receptor qPCR) using NB4 cells. One group of NB4 cells was treated with Alpha (PML-RARA) fusion protein. While most APL patients all-trans retinoic acid (ATRA) dissolved in dimethyl sulphoxide harbor the treatment-sensitive PML-RARA fusion protein, a (DMSO), while a control group was treated with DMSO only. subset of APL patients exhibit non-PML-RARA fusions which EBF3 expression was significantly decreased (p ▯ 0.01) in the are resistant to treatment. Recent bioinformatic and functional ATRA-treated cells compared to the control. This observation is analyses from my lab (Slack Lab) have identified EBF3 (Early B- expected because ATRA exerts its therapeutic effect through many Cell factor 3) as a gene whose transcription levels are significantmechanisms, including the degradation of PML-RARA. Since our elevated in patients with PML-RARA status. Given these data, we preliminary data suggest that PML-RARA may transcriptionally hypothesize that EBF3 contributes to the leukemic state in both upregulateEBF3,itsdegradationshouldleadtoadecreaseinEBF3 PML-RARA and non-PML-RARA APL by acting as an oncogene. expression. Thus, modulating EBF3 activity may serve as a new To investigate this further, our goal is to use cell-based assays ttherapeutictargetfortreatment-resistantAPLpatientsandimprove determine how EBF3 gene regulation contributes to the leukemic their treatment outcomes and survival rates. state in APL. We will also test the roles of PML-RARA on EBF3 106 Program for Research in Science and Engineering SuppressorAnalysisofConditionalMutantsfortheEssentialChaperoneCtr86 in Saccharomyces cerevisiae William Le, Marina Barba, Vlad Denic Churchill College, University of Cambridge | Molecular and Cellular Biology | 2026 Spinocerebellar ataxia type 10 (SCA10) is a neurodegenerative Cas9 based treatment. The purpose of this research is therefore disease affecting coordination associated with a pentanucleotide to screen for mutants in Saccharomyces cerevisiae that can (ATTCT) repeat expansion in the ATXN10 gene. Whilst bypass the essentiality of Ctr86 using two conditional yeast the specific function of ATXN10 (homologous to Ctr86 in mutant strains. Strategies for mutagenesis involve spontaneous Saccharomyces cerevisiae) is unknown, AlphaPulldown predicts suppressor accumulation, UV mutagenesis, and RLI1 plasmid a highly confident interaction between human ATXN10 and non- library production via error prone PCR. This is followed by native ABCE1 (homologous to Rli1 in Saccharomyces cerevisiae), validation steps such as replica plating, PCR, and protein suggesting ATXN10 may be involved in the folding of ABCE1. expression analysis. Compensatory mutations in the RLI1 locus, ABCE1/Rli1 is a highly conserved essential gene in eukaryotes the only known Ctr86 client, are currently being screened followed which facilitates ribosome dissociation following translational by whole genome sequencing to identify suppressor mutations at termination. Characterizing the activity of ATXN10/Ctr86 other loci. From this screen, we hope to identify key residues or as a chaperone of ABCE1/Rli1 is therefore important to domains in Rli1/Ctr86 required for folding of Rli1 as well as other characterizing the pathogenic mechanism of SCA10 and the potential interaction partners of Ctr86. development of future therapeutic treatments, such as CRISPR-
Source:
Harvard / Harvard College | Kirkland House | Applied Math | 2027 / 2025
Topics:
ebf3, pml, rli1, ctr86, apl, cell, treatment, atxn10, leukemia, gene, saccharomyce, cerevisiae
