title: FLT3 mutation and AML/ETO in a case of Myelodysplastic syndrome in transformation corroborates the two hit model of leukemogenesis.
abstract: The aim of this report is to present a case of Myelodysplastic syndrome (MDS) who presented, during AML transformation, a step-wise genetic progression that corroborates the two hit model of leukemogenesis. A RCDM-RS (WHO)/RARS (FAB) patient with normal karyotype at diagnosis, evolved into AML after six months of follow up. At transformation, AML/ETO fusion was detected, although marrow blast cells were not increased until 21 days later, when FLT3-ITD was also demonstrated pointing out that the overgrowth of the FLT3/ITD clone was concomitant with the outburst of marrow blasts. These findings corroborates the two hit model of leukemogenesis in which one class of mutations (Class I) (FLT3/ITD) confers a proliferative or survival advantage to cells, and a second class of mutations (Class II) (AML/ETO) interferes with hematopoietic differentiation.
authors.affiliation: Disciplina de Hematologia e Hemoterapia--Universidade Federal de São Paulo-UNIFESP-EPM, Brazil.
authors.forename: Ronald Feitosa
authors.initials: RF
authors.lastname: Pinheiro
authors.forename: Eloisa de Sá
authors.initials: Ede S
authors.lastname: Moreira
authors.forename: Maria Regina Régis
authors.initials: MR
authors.lastname: Silva
authors.forename: Bárbara
authors.initials: B
authors.lastname: Greggio
authors.forename: Fernando Lopes
authors.initials: FL
authors.lastname: Alberto
authors.forename: Maria de Lourdes L F
authors.initials: Mde L
authors.lastname: Chauffaille
mesh_terms: D001853:Bone Marrow / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D000075142:RUNX1 Translocation Partner 1 Protein; D020080:Tandem Repeat Sequences; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3