An MPL W515L mutation in refractory anemia with ringed sideroblasts associated with marked thrombocytosis: A case report
- Authors:
- Lin Hao
- Sandeep Sen
- Dhivya Sugumar
View Affiliations
Affiliations: Department of Internal Medicine, Saint Mary's Health Center, St. Louis, MO 63117, USA, SSM Cancer Care, Saint Mary's Health Center, St. Louis, MO 63117, USA
- Published online on: December 2, 2014 https://doi.org/10.3892/ol.2014.2754
-
Pages:
749-751
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Abstract
The current study presents the case of a 63‑year‑old patient exhibiting refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS‑T), who was positive for the MPL W515L mutation, but negative for the JAK2 V617F mutation. Following diagnosis, the patient remained asymptomatic for over three years, however, in August 2012, the patient relapsed and was administered with supportive treatment in the form of subcutaneous darbepoetin α at a dose of 300 µg/week, which resulted in an increased hemoglobin concentration, allowing the patient to remain transfusion‑independent. The MPL W515L mutation has been reported in two previous cases of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) with ringed sideroblasts, however, to the best of our knowledge, the current report is the first to present a case of RARS‑T with an MPL W515L mutation. A clinical trial designed to evaluate the efficacy of a targeted agent against the JAK2 V617F mutation is currently ongoing, with the aim of providing a novel therapeutic strategy for treating MDS/MPN patients. As MPL is located upstream of the JAK‑STAT signaling pathway, it is a possible therapeutic target in MDS/MPN patients positive for an MPL W515L mutation, but negative for a JAK2 V617F mutation.
View References
|
1
|
Vardiman JW, Bennett JM, Bain BJ, et al:
Myelodysplastic/myeloproliferative neoplasm, unclassifiable. WHO
Classification of Tumours of Haematopoietic and Lymphoid Tissues.
Swerdlow SH, Campo E, Harris NL, et al: 4th edition. IARC Press;
Lyon: pp. 85–86. 2008
|
|
2
|
Zikria J, Galili N, Tsai WY, et al:
Thrombocytosis in myelodysplastic syndromes: not an innocent
bystander. J Blood Disord Transfus. S3:0022012.
|
|
3
|
Schmitt-Graeff AH, Teo SS, Olschewski M,
et al: JAK2V617F mutation status identifies subtypes of refractory
anemia with ringed sideroblasts associated with marked
thrombocytosis. Haematologica. 93:34–40. 2008. View Article : Google Scholar : PubMed/NCBI
|
|
4
|
Greenberg P, Cox C, LeBeau MM, et al:
International scoring system for evaluating prognosis in
myelodysplastic syndromes. Blood. 89:2079–2088. 1997.PubMed/NCBI
|
|
5
|
Taylor G, Culligan D and Vickers MA:
Refractory anemia with ring sideroblasts associated with marked
thrombocytosis complicated by massive splenomegaly treated with
lenalidomide resulting in resolution of splenomegaly but severe and
prolonged pancytopenia. Case Rep Hemato. 2013:7184802013.
|
|
6
|
Vigon I, Mornon JP, Cocault L, et al:
Molecular cloning and characterization of MPL, the human homolog of
the v-mpl oncogene: identification of a member of the hematopoietic
growth factor receptor superfamily. Proc Natl Acad Sci USA.
89:5640–5644. 1992. View Article : Google Scholar : PubMed/NCBI
|
|
7
|
Pardanani AD, Levine RL, Lasho T, et al:
MPL515 mutations in myeloproliferative and other myeloid disorders:
a study of 1182 patients. Blood. 108:3472–3476. 2006. View Article : Google Scholar : PubMed/NCBI
|
|
8
|
Beer PA, Campbell PJ, Scott LM, et al: MPL
mutations in myeloproliferative disorders: analysis of the PT-1
cohort. Blood. 112:141–149. 2008. View Article : Google Scholar : PubMed/NCBI
|
|
9
|
Vannucchi AM, Antonioli E, Guglielmelli P,
et al: Characteristics and clinical correlates of MP 515W>L/K
mutation in essential thrombocythemia. Blood. 112:844–847. 2008.
View Article : Google Scholar : PubMed/NCBI
|
|
10
|
Schnittger S, Bacher U, Haferlach C, et
al: Detection of an MPLW515 mutation in a case with features of
both essential thrombocythemia and refractory anemia with ringed
sideroblasts and thrombocytosis. Leukemia. 22:453–455. 2008.
View Article : Google Scholar
|
|
11
|
Tefferi A: Novel mutations and their
functional and clinical relevance in myeloproliferative neoplasms:
JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia. 24:1128–1138.
2010. View Article : Google Scholar : PubMed/NCBI
|
|
12
|
Pikman Y, Lee BH, Mercher T, et al:
MPLW515L is a novel somatic activating mutation in myelofibrosis
with myeloid metaplasia. PLoS Med. 3:e2702006. View Article : Google Scholar : PubMed/NCBI
|
