Reproductive fitness advantage of BCR-ABL expressing leukemia cells.
Mutations in oncogenes and tumor suppressor genes confer a fitness advantage to cells that can lead to cancer. The tumor phenotype normally results from the interaction of many mutant genes making it difficult to estimate the fitness advantage provided by any oncogene, except when tumors depend on one oncogene only. We utilize a model of chronic myeloid leukemia (CML), to quantitate the fitness advantage conferred by expression of BCR-ABL in hematopoietic cells from in vivo patient data. We show that BCR-ABL expression provides a high fitness advantage, which explains why this single mutation drives the chronic phase of CML.
Emmy-Noether Group for Evolutionary Dynamics, Max Planck Institute for Evolutionary Biology, Plön, Germany.
Arne
A
Traulsen
Jorge M
JM
Pacheco
David
D
Dingli
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D056084:Genetic Fitness; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D009857:Oncogenes; D010641:Phenotype; D010879:Piperazines / Q000627:therapeutic use; D011336:Probability; D011743:Pyrimidines / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl