Polycythemia vera transforming to acute myeloid leukemia and complex abnormalities including 9p homogeneously staining region with amplification of MLLT3, JMJD2C, JAK2, and SMARCA2.
Polycythemia vera (PV) is a clonal stem cell disorder characterized by an excessive erythrocyte production. At diagnosis, a normal karyotype is found in < or =80% of cases, but an abnormal karyotype frequently develops with evolution. Trisomy 9 and gains on 9p are some of the most frequent cytogenetic abnormalities, together with trisomy 8 and del(20q) in both PV and idiopathic myelofibrosis. We report the case of a 54-year-old man whose disease was classified as an acute myeloid transformation of PV. Cytogenetic and multicolor fluorescence in situ hybridization (FISH) analysis detected several chromosomal abnormalities that included an amplification of 9p. Complementary FISH analysis established amplification of the 9p22 approximately p24.3 region including several known genes: MLLT3 (alias AF9), JMJD2C (alias GASC1), JAK2, and SMARCA2 (alias BRM). JAK2(V617F) mutation status was quantitatively assessed by allele-specific quantitative polymerase chain reaction. Although crossing points analysis showed JAK2(V617F) mutated alleles at 52%, it is still impossible to describe conclusively the mutational status of the amplified JAK2 gene within the sole homogeneously staining region, because total genomic DNA was extracted for the analysis and not only DNA from cells with the homogeneously staining region. Gains on 9p being among the most common anomalies in PV, amplification of a gene or genes on this region may play a crucial role in the pathogenesis or evolution of PV.
Hélias
Catherine
C
Laboratory of Hematology, Hautepierre Hospital, Avenue Molière, Strasbourg 67098, France. catherine.helias@chru-strasbourg.fr
Struski
Stephanie
S
Gervais
Carine
C
Leymarie
Vincent
V
Mauvieux
Laurent
L
Herbrecht
Raoul
R
Lessard
Michel
M
D002869:Chromosome Aberrations; D002899:Chromosomes, Human, Pair 9; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053614:Janus Kinase 2 / Q000235:genetics*; D056484:Jumonji Domain-Containing Histone Demethylases; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011087:Polycythemia Vera / Q000150:complications*; D014157:Transcription Factors / Q000235:genetics*
C413655:KDM4C protein, human; C489901:MLLT3 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C084011:SMARCA2 protein, human; D014157:Transcription Factors; D056484:Jumonji Domain-Containing Histone Demethylases; C507924:JAK2 protein, human; D053614:Janus Kinase 2