TY - JOUR
T1 - 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
AU - Gu, Jun
AU - Patel, Keyur P.
AU - Bai, Bing
AU - Liu, Ching Hua
AU - Tang, Guilin
AU - Kantarjian, Hagop M.
AU - Tang, Zhenya
AU - Abraham, Ronald
AU - Luthra, Rajyalakshmi
AU - Medeiros, L. Jeffrey
AU - Lin, Pei
AU - Lu, Xinyan
N1 - Publisher Copyright:
© 2015 Gu et al.
PY - 2015/8/19
Y1 - 2015/8/19
N2 - 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.
AB - 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.
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U2 - 10.1186/s13039-015-0171-2
DO - 10.1186/s13039-015-0171-2
M3 - Article
C2 - 26300976
AN - SCOPUS:84939423170
SN - 1755-8166
VL - 8
JO - Molecular Cytogenetics
JF - Molecular Cytogenetics
IS - 1
M1 - 68
ER -