Molecular characterization of complex chromosomal changes in de novo acute myeloid leukemia: a case report

Abstract De novo acute myeloid leukemias (AML) represent a heterogeneous group of clonal hematopoietic disorders in which chromosomal abnormalities are detected in a majority of patients. At present, cytogenetic changes are recognized as important diagnostic markers and prognosis determinants. Complex karyotype changes are associated with resistance to treatment and unfavorable evolution. We report on an AML case with complex karyotype changes characterized by molecular genetic techniques (fluorescence in situ hybridization - FISH and array-based comparative genomic hybridization - array-CGH) and an extremely poor outcome. A 72 year-old female patient was admitted for genetic investigations with a clinical diagnosis of AML. Classical and molecular cytogenetic tests as well as array-CGH were performed. Complex chromosomal abnormalities were identified at diagnosis, consisting of genomic imbalances involving chromosomes 6, 7, 9, and 17. AML with complex karyotype changes is a heterogeneous disease, as a variety of genomic abnormalities are detected, involving virtually all chromosomes. The pathogenesis of AML with complex karyotype is poorly understood. The complexity of karyotypic changes in our case highlights the importance of using complementary genetic investigation in order to obtain a comprehensive view of AML genome. Rezumat Leucemiile mieloide acute de novo (LAM) reprezintă un grup heterogen de afecţiuni hematopoietice clo- nale, majoritatea pacienţilor prezentând anomalii cromozomiale. Modificările citogenetice sunt considerate în momentul actual factori importanţi de diagnostic şi prognostic. Modificările complexe ale cariotipului sunt aso- ciate cil rezistenţa la tratament şi evoluţie nefavorabilă. Raportăm cazul unei paciente cu AML şi modificări complexe de cariotip identificate prin tehnici citogenetice şi moleculare (hibridizare in situ fluorescentă - FISH şi hibridizare comparativa genomică bazata pe microarray - array-CGH) la care evoluţia a fost extrem de nefa- vorabila. Pacientei, în vârsta de 72 de ani, i-aufost recomandate investigaţii citogenetice în contextul unui diag- nostic clinic şi hematologic de LAM. Au fost efectuate teste citogenetice şi moleculare, incluzând array-C.GH. Au fost identificate modificări cromozomiale complexe reprezentate de dezechilibre genomice implicând cromozomii 6, 7, 9 şi 17. Pacienţii cu LAM cu modificări complexe de cariotip reprezintă un grup heterogen, la care sunt de- tectate numeroase anomalii genomice ce pot afecta practic orice cromozom. Patogeneza LAM cu cariotip com- plex este incomplet înţeleasă. Complexitatea modificărilor genetice la pacienta noastră subliniază importanţa utilizării de investigaţii genetice complementare pentru a obţine o imagine cât mai comprehensivă a anomaliilor genomice la pacienţii cu LAM.