Abstract
BACKGROUND:
Hematopoietic malignancies are a group of blood cell disorders characterized by abnormal hematopoietic proliferation.
OBJECTIVE:
The identification of specific clinicopathologic characteristics and tumor-related gene status provides critical information on potential therapeutic targets.
METHODS:
The specimens were tested with immunohistochemistry, flow cytometry, RT-PCR and fragment analysis.
RESULTS:
In this study, a patient with a long history of tobacco use was reported with a diagnosis of simultaneous low-grade B-cell lymphoproliferative disorder (LPD) and myeloproliferative neoplasm (MPN). Mutational analysis revealed that JAK2 V617F mutation and CALR mutation with 52bp deletion were present in this patient.
CONCLUSION:
These results suggest that lymphoproliferative and myeloproliferative neoplasms may coexist, although the pathogenetic mechanism of coexisting hematologic requires further investigation. Additionally, the data indicate that JAK2 V617F and CALR mutations are not mutually exclusive and the actual frequency of simultaneous JAK2 V617F and CALR mutations is unknown. Whether the coexistence of these mutations imposes any biological or clinical significance awaits further investigation.
Keywords: Lymphoproliferative neoplasm, MPNs, JAK2, CALR
References
- [1]. Vardiman JW: The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues: An overview with emphasis on the myeloid neoplasms. Chemico-Biological Interactions 2010, 184(1-2): 16-20. [DOI] [PubMed] [Google Scholar]
- [2]. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC: A gain-of-function mutation of JAK2 in myeloproliferative disorders. The New England Journal of Medicine 2005, 352(17): 1779-1790. [DOI] [PubMed] [Google Scholar]
- [3]. Kralovics R, Teo SS, Buser AS, Brutsche M, Tiedt R, Tichelli A, Passamonti F, Pietra D, Cazzola M, Skoda RC: Altered gene expression in myeloproliferative disorders correlates with activation of signaling by the V617F mutation of Jak2. Blood 2005, 106(10): 3374-3376. [DOI] [PubMed] [Google Scholar]
- [4]. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D et al.: Somatic mutations of calreticulin in myeloproliferative neoplasms. The New England Kournal of Medicine 2013, 369(25): 2379-2390. [DOI] [PubMed] [Google Scholar]
- [5]. Rumi E, Pietra D, Ferretti V, Klampfl T, Harutyunyan AS, Milosevic JD, Them NC, Berg T, Elena C, Casetti IC et al.: JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood 2014, 123(10): 1544-1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [6]. Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG et al.: Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. The New England Journal of Medicine 2013, 369(25): 2391-2405. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [7]. Rotunno G, Mannarelli C, Guglielmelli P, Pacilli A, Pancrazzi A, Pieri L, Fanelli T, Bosi A, Vannucchi AM, Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative I: Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood 2014, 123(10): 1552-1555. [DOI] [PubMed] [Google Scholar]
- [8]. Rumi E, Pietra D, Pascutto C, Guglielmelli P, Martinez-Trillos A, Casetti I, Colomer D, Pieri L, Pratcorona M, Rotunno G et al.: Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood 2014, 124(7): 1062-1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9]. Lee SH, Erber WN, Porwit A, Tomonaga M, Peterson LC, International Council for Standardization In H: ICSH guidelines for the standardization of bone marrow specimens and reports. International Journal of Laboratory Hematology 2008, 30(5): 349-364. [DOI] [PubMed] [Google Scholar]
- [10]. Broseus J, Lippert E, Harutyunyan AS, Jeromin S, Zipperer E, Florensa L, Milosevic JD, Haferlach T, Germing U, Luno E et al.: Low rate of calreticulin mutations in refractory anaemia with ring sideroblasts and marked thrombocytosis. Leukemia 2014, 28(6): 1374-1376. [DOI] [PubMed] [Google Scholar]
- [11]. Lundberg P, Karow A, Nienhold R, Looser R, Hao-Shen H, Nissen I, Girsberger S, Lehmann T, Passweg J, Stern M et al.: Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood 2014, 123(14): 2220-2228. [DOI] [PubMed] [Google Scholar]
- [12]. McGaffin G, Harper K, Stirling D, McLintock L: JAK2 V617F and CALR mutations are not mutually exclusive; findings from retrospective analysis of a small patient cohort. British Journal of Haematology 2014, 167(2): 276-278. [DOI] [PubMed] [Google Scholar]
- [13]. Tefferi A, Lasho TL, Finke CM, Knudson RA, Ketterling R, Hanson CH, Maffioli M, Caramazza D, Passamonti F, Pardanani A: CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia 2014, 28(7): 1472-1477. [DOI] [PubMed] [Google Scholar]