title: Double inv(3)(q21q26.2) in acute myeloid leukemia is resulted from an acquired copy neutral loss of heterozygosity of chromosome 3q and associated with disease progression.
abstract: BACKGROUND
  Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) is a distinct clinicopathologic entity with a poor prognosis. However, double inv(3)(q21q26.2) is extremely rare in AML. We report here 3 cases analyzed by oligonucleotide microarray comparative genomic hybridization (aCGH) and single nucleotide polymorphism (SNP). Clinicopathologic, cytogenetic and molecular findings were correlated with clinical outcome to better understand the entity.
  
  
  RESULTS
  The study group included one man and two women at 56-74 years of age. The AML arose from myelodysplastic syndrome in one patient and from chronic myelomonocytic leukemia in another patient. Monosomy 7 was found as additional cytogenetic finding in one patient. One patient had a single inv(3) in the initial clone and acquired double inv(3) as part of clonal evolution. EVI1 (MECOM) rearrangement was confirmed using metaphase/interphase fluorescence in situ hybridization (FISH). Microarray (aCGH + SNP) data analysis revealed that the double inv(3) was a result of acquiring copy neutral loss of heterozygosity of chromosome 3q: arr[hg19] 3q13.21q29(10,344,387-197,802,470)x2 hmz, spanning ~ 94.3 Mb in size. Mutational profiling showed a PTPN11 mutation at a low level (~10 %) in one patient and wild type FLT3 and RAS in all patients. No patients achieved cytogenetic remission and all died with an overall survival (OS) of 23, 12 and 5 months, respectively.
  
  
  CONCLUSIONS
  Double inv(3) is a result of acquired copy neutral loss of heterozygosity, a somatic repair event occurring as a part of mitotic recombination of the partial chromosome 3q. The double inv(3) in AML patients is highly associated with a rapid disease progression.
authors: Cytogenetic Technology Program, School of Health Professions, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0002, Houston, TX 77030 USA.
authors: Jun
authors: J
authors: Gu
authors: The Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0149, Houston, TX 77030 USA.
authors: Keyur P
authors: KP
authors: Patel
authors: The Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0149, Houston, TX 77030 USA.
authors: Bing
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authors: Bai
authors: Cytogenetic Technology Program, School of Health Professions, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0002, Houston, TX 77030 USA ; The Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0149, Houston, TX 77030 USA.
authors: Ching-Hua
authors: CH
authors: Liu
authors: The Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0149, Houston, TX 77030 USA.
authors: Guilin
authors: G
authors: Tang
authors: Department of Leukemia, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0428, Houston, TX 77030 USA.
authors: Hagop M
authors: HM
authors: Kantarjian
authors: The Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0149, Houston, TX 77030 USA.
authors: Zhenya
authors: Z
authors: Tang
authors: The Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0149, Houston, TX 77030 USA.
authors: Ronald
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authors: Abraham
authors: The Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0149, Houston, TX 77030 USA.
authors: Rajyalakshmi
authors: R
authors: Luthra
authors: The Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0149, Houston, TX 77030 USA.
authors: L Jeffrey
authors: LJ
authors: Medeiros
authors: The Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0149, Houston, TX 77030 USA.
authors: Pei
authors: P
authors: Lin
authors: The Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0149, Houston, TX 77030 USA.
authors: Xinyan
authors: X
authors: Lu