|LETTER TO THE EDITOR
|Year : 2017 | Volume
| Issue : 2 | Page : 46-50
In the era of next generation sequencing, is the cytogenetic analysis still important in polycythemia vera?
Prakas Kumar Mandal, S Kartthik
Department of Hematology, N.R.S. Medical College and Hospital, Kolkata, West Bengal, India
|Date of Web Publication||22-Jun-2017|
Prakas Kumar Mandal
Department of Hematology, N.R.S. Medical College and Hospital, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Mandal PK, Kartthik S. In the era of next generation sequencing, is the cytogenetic analysis still important in polycythemia vera?. South Asian J Cancer 2017;6:46-50
|How to cite this URL:|
Mandal PK, Kartthik S. In the era of next generation sequencing, is the cytogenetic analysis still important in polycythemia vera?. South Asian J Cancer [serial online] 2017 [cited 2020 Jan 17];6:46-50. Available from: http://journal.sajc.org/text.asp?2017/6/2/46/208843
Polycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) characterized by increased red blood cell production. WHO 2008 criteria for PV diagnosis are based on laboratory, morphological, and molecular findings. Microsatellite studies on chromosome nine identified acquired uniparental disomy (UPD) as a common defect in MPN. V617F mutation in the Janus kinase 2 gene (JAK2) present in 95% of PV and >50% of essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients. New target gene CBL is associated with aberrations of chromosome 11q. CBL exons 8 and 9 (11q23.3) mutations seen commonly in PMF and post MPN and rarer in PV and ET. Here we report a case of PV with 11q23 deletion with a stable disease.
A 70-year-old male presented with pruritus for 1 year. Hemoglobin was 211 g/L, hematocrit-68.5%, total leucocyte count−20.6 × 106/L, platelet count−470 × 109/L with neutrophilic leukocytosis. Bone marrow was hypercellular with trilineage hyperplasia. Serum erythropoietin was 1.2 mIU/ml and JAK2 V617F from peripheral blood was positive. Cytogenetic analysis showed 46, XY with 11q23 deletion in 100% cells [Figure 1]. He was started on biweekly phlebotomy, aspirin 75 mg once daily and hydroxyurea 500 mg once daily; maintaining a hematocrit of 45% and off phlebotomy for the last 8 months.
|Figure 1: Cytogenetic analysis following unstimulated cell culture and GTG-banding revealed 46, XY, del (11q23) chromosomal pattern in all (100%) cells examined|
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Cytogenetic abnormalities in PV being del (20q), del (13q), +8, +9 and chromosome 1 abnormalities and acquired UPD of 1p, 4q 7q, 9p, and 11q associated with homozygosity for mutations in MPL, TET2, EZH2, JAK2 and CBL respectively. CBL mutations in myeloid malignancies are associated with 11q acquired UPD. The present case compared with cases from other studies with chromosome 11 abnormalities in [Table 1]. It's apparent from the literature that PV with chromosome 11 abnormalities has a chance of progression to AML. Hence, our index case has to be kept on close follow-up. Next generation sequencing based identification of molecular markers indicating progression, are mostly not available in resource constrain countries like India. Therefore, one may still use conventional cytogenetics to indicate the molecular change responsible for progression.
|Table 1: Comparison of present case with previous studies showing chromosome 11 abnormalities|
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Klampfl T, Harutyunyan A, Berg T, Gisslinger B, Schalling M, Bagienski K, et al
. Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression. Blood 2011;118:167-76.
Gangat N, Strand J, Lasho TL, Finke CM, Knudson RA, Pardanani A, et al. Cytogenetic studies at diagnosis in polycythemia vera: Clinical and JAK2V617F allele burden correlates. Eur J Haematol 2008;80:197-200.
Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia 2010;24:1128-38.
Klampfl T, Milosevic JD, Puda A, Schönegger A, Bagienski K, Berg T, et al
. Complex patterns of chromosome 11 aberrations in myeloid malignancies target CBL, MLL, DDB1 and LMO2. PLoS One 2013;8:e77819.
Sever M, Quintás-Cardama A, Pierce S, Zhou L, Kantarjian H, Verstovsek S. Significance of cytogenetic abnormalities in patients with polycythemia vera. Leuk Lymphoma 2013;54:2667-70.