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(Paper co-edited with the European LeukemiaNet)
Unbalanced rearrangement der(9;18)(p10;q10) and JAK2 V617F mutation in a patient with AML following post-polycythemic myelofibrosis
Written2011-09Francesca Cambosu, Giuseppina Fogu, Paola Maria Campus, Claudio Fozza, Luigi Podda, Andrea Montella, Maurizio Longinotti
Clinical Genetics, Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B 07100 Sassari, Italy (FC, GF, AM); Azienda Ospedaliero-Universitaria Sassari, Italy (PMC, CF, LP, AM, ML); Institute of Hematology, University of Sassari, Italy (CF, LP, ML)
Age and sex : 66 year(s) old male patient.
Previous History : no preleukemia
no previous malignant disease
no inborn condition of note
Polycythemia vera in 1980. Myelofibrosis in progression in Feb. 2008. AML M2 FAB in Dec. 2008.
Organomegaly : hepatomegaly (enlarged liver (+ 20 cm)); splenomegaly ; no enlarged lymph nodes ; no central nervous system involvement
WBC : 46 x 109/L ; Hb : 8.5 g/dL ; platelets : 239 x 109/L; blasts : 15 % .
Bone marrow : 25
Cyto pathology classification
Cytology : NA
Immunophenotype : NA
Rearranged Ig Tcr : NA
Pathology : NA
Electron microscopy : NA
Precise diagnosis : Polycythemia vera. Myelofibrosis: hypocellular bone marrow with marked increase in reticulin fibres. AML M2.
Date of diagnosis: 01-1980
Treatment : Bleeding therapy and acethylsalicylic acid. 2005 -2008: Etanercept (anti-TNF alpha). 2007: Hydroxyurea. Sept. 2008: Splenectomy. Feb. 2008: Pomalidomide, suspended after 1 month because of a severe neutropeny. Feb 2009: Bone Marrow allograft.
Complete remission : None
Treatment related death : -
Relapse : -
Status : Dead 11-2010 (due to gastrointestinal hemorrhage)
Survival : 360 month(s)
Sample : Bone marrow biopsy in Dec. 2008 ; culture time : 24 h, and 48 h. ; banding : Cytogenetic analysis performed in QFQ banding; band level: 400.
Results : 46,XY, +9,der(9;18)(p10;q10) in 25/25 cells scored.
Probes: whole-chromosome painting probes (wcp) and centromeric (CEP) probes of chromosomes 9 (9p11-q11 alpha satellite DNA) and 18 (D18Z1) (Abbott Molecular/Vysis).
Polycythemia Vera (PV) is a clonal myeloproliferative disorder characterized by excessive erythrocyte production, which may evolve into myelofibrosis and acute myeloid leukemia. Transformation to myelofibrosis occurs in 15-20% of cases and leukemic transformation in 5-10% of patients. The median survival time is 8-11 years and the median age at diagnosis is over 60 years. Normal karyotype is present at diagnosis in the majority of patients, while during transformation several acquired chromosome anomalies are present as trisomy 9 and gains in 9p.
The activating JAK2 V617F mutation, present in the majority of patients with PV, seems to have a primary role in the pathogenesis of myeloproliferative neoplasms. The JAK2 gene maps to 9p24, so patients carrying gains of 9p have an extra copy of the gene, in its normal or mutated form, leading to a gain of function.
The rearrangement here reported, der(9;18)(p10;q10), is rarely detected in patients with PV, myelofibrosis, essential thrombocythemia and therapy-related AML. Some authors suggest that the simultaneous presence of both JAK2 V617F mutation and this rearrangement could define a subgroup of PV patients with the proliferative phenotype of the disease, at high risk of transformation into postpolycythemic myelofibrosis and potentially acute myeloid leukemia.
We describe a new case of der(9;18)(p10;q10) detected in a patient with AML evolved from post-polycythemic myelofibrosis. The patient was diagnosed with PV in 1980 and died in 2010. He was in good health for several years after diagnosis with bleeding treatment and low dose aspirin, then he showed a progressive worsening of anemia with liver enlargement and splenomegaly. In February 2008 the diagnosis was of myelofibrosis post PV in progression. In December 2008, when the leukemic transformation was evident, the cytogenetic analysis on bone marrow aspirate found the unbalanced translocation leading to der(9;18)(p10;q10), with trisomy of the short arms of chromosome 9 and monosomy of the short arms of chromosome 18. FISH experiments with specific alphoid centromeric probes for chromosome 9 and 18 showed both positive signals on the der(9). Subsequent molecular analysis detected the presence of the JAK2 V617F mutation.
The patient here reported had a classical evolution of the disease, after a very long polycythemic phase with a noteworthy survival time likely correlated to the young age of the patient when PV occurred. Because of the absence of cytogenetic results at diagnosis and during the polycythemic phase, we cannot fully evaluate the significance of der(9;18)(p10;q10) in the natural history of the disease before its evolution. Future reports could make clear this not negligible aspect.
Internal links
Atlas Cardder(9;18)(p10;q10)
Case ReportUnbalanced rearrangement der(9;18)(p10;q10) in a patient with polycythemia vera
Case ReportUnbalanced rearrangement, der(9;18)(p10;q10) in a patient with myeloproliferative neoplasm. Case 0001M
Case ReportUnbalanced rearrangement, der(9;18)(p10;q10) in a patient with myelodysplastic syndrome. Case 0002M
Gain of 9p in the pathogenesis of polycythemia vera.
Chen Z, Notohamiprodjo M, Guan XY, Paietta E, Blackwell S, Stout K, Turner A, Richkind K, Trent JM, Lamb A, Sandberg AA.
Genes Chromosomes Cancer. 1998 Aug;22(4):321-4.
PMID 9669670
Karyotypic abnormalities in myelofibrosis following polycythemia vera.
Andrieux J, Demory JL, Caulier MT, Agape P, Wetterwald M, Bauters F, Lai JL.
Cancer Genet Cytogenet. 2003 Jan 15;140(2):118-23.
PMID 12645649
Gain of 9p due to an unbalanced rearrangement der(9;18): a recurrent clonal abnormality in chronic myeloproliferative disorders.
Bacher U, Haferlach T, Schoch C.
Cancer Genet Cytogenet. 2005 Jul 15;160(2):179-83.
PMID 15993276
A der(18)t(9;18)(p13;p11) and a der(9;18)(p10;q10) in polycythemia vera associated with a hyperproliferative phenotype in transformation to postpolycythemic myelofibrosis.
Larsen TS, Hasselbalch HC, Pallisgaard N, Kerndrup GB.
Cancer Genet Cytogenet. 2007 Jan 15;172(2):107-12.
PMID 17213018
Recurrent der(9;18) in essential thrombocythemia with JAK2 V617F is highly linked to myelofibrosis development.
Ohyashiki K, Kodama A, Ohyashiki JH.
Cancer Genet Cytogenet. 2008 Oct;186(1):6-11.
PMID 18786436
Unbalanced rearrangement der(9;18)(p10;q10) in a patient with polycythemia vera.
Xu X, Chen X, Rauch EA, Johnson EB, Thompson KJ, Laffin JJS, Raca G, Kurtycz DF.
Atlas Genet Cytogenet Oncol Haematol. April 2010. URL: .


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