What do functional genomics tell us about pathogenesis of AML?

Research output: Contribution to journalReview article

Abstract

While molecular genetic abnormalities can tell us much about the pathogenesis of acute myeloid leukemia (AML), these molecular genetics do not always explain drug resistance or sensitivity, leaving room for other mechanisms of tumor pathogenesis outside of genetic events. The Beat AML 1.0 project was a multicenter project to sequence and functionally query AML samples against over 120 drugs. The results have helped form disease models on how mutations affect disease phenotype and drug sensitivity and have assisted in identifying gene signature profiles that may facilitate selecting the most effective treatment options. However, there are factors outside of genetic abnormalities that affect disease pathogenesis. For example, tumor-associated macrophages in the tumor microenvironment play a role in pathogenesis and represent therapeutic targets.

Original languageEnglish (US)
Article number101101
JournalBest Practice and Research: Clinical Haematology
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Genomics
Acute Myeloid Leukemia
Tumors
Molecular Biology
Pharmaceutical Preparations
Tumor Microenvironment
Macrophages
Drug Resistance
Neoplasms
Genes
Phenotype
Mutation
Therapeutics

Keywords

  • Acute myeloid leukemia
  • AML
  • Beat AML 1.0
  • Microenvironment
  • Pathogenesis
  • Tumor-associated macrophage

ASJC Scopus subject areas

  • Oncology
  • Clinical Biochemistry

Cite this

@article{58fd6332b4494e2891fdf258773d7cec,
title = "What do functional genomics tell us about pathogenesis of AML?",
abstract = "While molecular genetic abnormalities can tell us much about the pathogenesis of acute myeloid leukemia (AML), these molecular genetics do not always explain drug resistance or sensitivity, leaving room for other mechanisms of tumor pathogenesis outside of genetic events. The Beat AML 1.0 project was a multicenter project to sequence and functionally query AML samples against over 120 drugs. The results have helped form disease models on how mutations affect disease phenotype and drug sensitivity and have assisted in identifying gene signature profiles that may facilitate selecting the most effective treatment options. However, there are factors outside of genetic abnormalities that affect disease pathogenesis. For example, tumor-associated macrophages in the tumor microenvironment play a role in pathogenesis and represent therapeutic targets.",
keywords = "Acute myeloid leukemia, AML, Beat AML 1.0, Microenvironment, Pathogenesis, Tumor-associated macrophage",
author = "Tyner, {Jeffrey W.} and Daniel Bottomly and Beth Wilmot and Shannon McWeeney",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.beha.2019.101101",
language = "English (US)",
journal = "Best Practice and Research in Clinical Haematology",
issn = "1521-6926",
publisher = "Bailliere Tindall Ltd",

}

TY - JOUR

T1 - What do functional genomics tell us about pathogenesis of AML?

AU - Tyner, Jeffrey W.

AU - Bottomly, Daniel

AU - Wilmot, Beth

AU - McWeeney, Shannon

PY - 2019/1/1

Y1 - 2019/1/1

N2 - While molecular genetic abnormalities can tell us much about the pathogenesis of acute myeloid leukemia (AML), these molecular genetics do not always explain drug resistance or sensitivity, leaving room for other mechanisms of tumor pathogenesis outside of genetic events. The Beat AML 1.0 project was a multicenter project to sequence and functionally query AML samples against over 120 drugs. The results have helped form disease models on how mutations affect disease phenotype and drug sensitivity and have assisted in identifying gene signature profiles that may facilitate selecting the most effective treatment options. However, there are factors outside of genetic abnormalities that affect disease pathogenesis. For example, tumor-associated macrophages in the tumor microenvironment play a role in pathogenesis and represent therapeutic targets.

AB - While molecular genetic abnormalities can tell us much about the pathogenesis of acute myeloid leukemia (AML), these molecular genetics do not always explain drug resistance or sensitivity, leaving room for other mechanisms of tumor pathogenesis outside of genetic events. The Beat AML 1.0 project was a multicenter project to sequence and functionally query AML samples against over 120 drugs. The results have helped form disease models on how mutations affect disease phenotype and drug sensitivity and have assisted in identifying gene signature profiles that may facilitate selecting the most effective treatment options. However, there are factors outside of genetic abnormalities that affect disease pathogenesis. For example, tumor-associated macrophages in the tumor microenvironment play a role in pathogenesis and represent therapeutic targets.

KW - Acute myeloid leukemia

KW - AML

KW - Beat AML 1.0

KW - Microenvironment

KW - Pathogenesis

KW - Tumor-associated macrophage

UR - http://www.scopus.com/inward/record.url?scp=85074167693&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074167693&partnerID=8YFLogxK

U2 - 10.1016/j.beha.2019.101101

DO - 10.1016/j.beha.2019.101101

M3 - Review article

AN - SCOPUS:85074167693

JO - Best Practice and Research in Clinical Haematology

JF - Best Practice and Research in Clinical Haematology

SN - 1521-6926

M1 - 101101

ER -