title: A method to identify new molecular markers for assessing minimal residual disease in acute leukemia patients.
abstract: Acute leukemias (AL) comprise a heterogeneous group of hematologic malignancies, and individual patient responses to treatment can be difficult to predict. Monitoring of minimal residual disease (MRD) is thus very important and holds great potential for improving treatment strategies. Common MRD targets include recurrent cytogenetic abnormalities and mutations in important hematological genes; unfortunately well-characterized targets are lacking in many AL patients. Here we demonstrate a technical approach for the identification and mapping of novel clone-specific chromosomal abnormalities down to the nucleotide level. We used molecular cytogenetics, chromosome microdissection, amplification of the microdissected material, and next-generation sequencing to develop PCR-based MRD assays based on unique breakpoint sequences.
authors.affiliation: Chambon, Laboratory for Molecular Diagnostics, Prague, Czech Republic.
authors.forename: Tereza
authors.initials: T
authors.lastname: Jancuskova
authors.forename: Radek
authors.initials: R
authors.lastname: Plachy
authors.forename: Jiri
authors.initials: J
authors.lastname: Stika
authors.forename: Lucie
authors.initials: L
authors.lastname: Zemankova
authors.forename: David W
authors.initials: DW
authors.lastname: Hardekopf
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.forename: Nadezda
authors.initials: N
authors.lastname: Kosyakova
authors.forename: Radek
authors.initials: R
authors.lastname: Cmejla
authors.forename: Lenka
authors.initials: L
authors.lastname: Zejskova
authors.forename: Tomas
authors.initials: T
authors.lastname: Kozak
authors.forename: Pavel
authors.initials: P
authors.lastname: Zak
authors.forename: Alzbeta
authors.initials: A
authors.lastname: Zavrelova
authors.forename: Pavlina
authors.initials: P
authors.lastname: Havlikova
authors.forename: Michal
authors.initials: M
authors.lastname: Karas
authors.forename: Annelore
authors.initials: A
authors.lastname: Junge
authors.forename: Christian
authors.initials: C
authors.lastname: Ramel
authors.forename: Sona
authors.initials: S
authors.lastname: Pekova
mesh_terms: D059786:Abnormal Karyotype; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D056905:Chromosome Breakpoints; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000175:diagnosis* / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D035602:Transcriptional Elongation Factors
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D035602:Transcriptional Elongation Factors; D051788:Myeloid-Lymphoid Leukemia Protein; C081449:AFF1 protein, human; D011495:Histone-Lysine N-Methyltransferase
keywords: Acute leukemia; Chromosome microdissection; Cytogenetics; Minimal residual disease; Next-generation sequencing; Personalized medicine