The JAK2 V617F mutation identifies a subgroup of MDS patients with isolated deletion 5q and a proliferative bone marrow

Ingram, Wendy; Lea, Nicholas; Cervera, José; Germing, Ulrich; Fenaux, Pierre; Cassinat, Bruno; Kiladjian, Jean‐Jacques; Varkonyi, J; Antunović, Petar; Westwood, Nigel; Arno, Matthew; Mohamedali, Azim; Gäken, Joop; Kontou, Trisevgeni; Czepulkowski, Barbara; Twine, Natalie A.; Tamáska, Júlia; Csomer, J; Benedek, Szabolcs; Gattermann, Norbert; Zipperer, Esther; Giagounidis, Aristoteles; García-Casado, Zaida; Sanz, Guillermo; Mufti, Ghulam J.

doi:10.1038/sj.leu.2404215

Cited by 89 publications

(61 citation statements)

References 8 publications

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“…41 The JAK2V617F mutated cases of this study were mainly categorized as MDS/MPN overlap or RARS-T, confirming previous observations. 42,43 Corresponding to previous reports on the occurrence of the FLT3-ITD in MDS being associated with leukemic transformation, we here observed this molecular marker in MDS-RAEB or CMML cases only. 21,22 However, with the exception of RUNX1, a standard screening for the other mutations in MDS cannot be recommended, but should be initiated according to clinical relevance and morphology.…”

Section: Diagnostic Workup Of Mds/bacher Et Alsupporting

confidence: 54%

The impact of cytomorphology, cytogenetics, molecular genetics, and immunophenotyping in a comprehensive diagnostic workup of myelodysplastic syndromes

Bacher

Haferlach

Kern

et al. 2009

Cancer

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These supportive care recommendations were prepared to guide doctors who practice in areas with significantly limited resources but who have sufficient infrastructure and training to treat children with cancer with curative intent. The success of any cancer treatment regimen depends largely on the availability and quality of supportive care and this also determines the intensity of treatment that can be delivered. We present practical recommendations on how to prevent infections, general nursing care, management of febrile neutropenia, nutritional assessment and support, treatment of co‐infections and the social support to help prevent failure to complete treatment in resource poor settings. Pediatr Blood Cancer 2013; 60: 899–904. © 2013 Wiley Periodicals, Inc.

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Section: Diagnostic Workup Of Mds/bacher Et Alsupporting

confidence: 54%

The impact of cytomorphology, cytogenetics, molecular genetics, and immunophenotyping in a comprehensive diagnostic workup of myelodysplastic syndromes

Bacher

Haferlach

Kern

et al. 2009

Cancer

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“…The concomitant presence of the 5q deletion and a JAK2 V617F mutation in MDS was first shown in 6/97 patients with MDS with the 5q deletion (6). Patients harboring the JAK2 V617F mutation compared to those without the mutation, presented with hypercellular bone marrow and exhibited significantly higher levels of WBC count and a trend towards higher levels of platelet count (6). Since the clinical outcome of this subset of patients remains unclear, the 2008 WHO classification classifies them as MDS with isolated del(5q), rather than in the MDS/MPN category.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of this mutation has also been described in other hematological malignancies, however, to a much lesser extent; ~3-5% of patients with MDS and <5% of patients with acute myeloid leukemia (AML) (5). The coexistence of del(5q) as sole cytogenetic abnormality and the JAK2 V617F mutation is even rarer occurring in a small subset of del(5q) MDS cases, and the optimal therapeutic approach in these patients remains to be elucidated (6).…”

Section: Introductionmentioning

confidence: 99%

Durable response to lenalidomide in a patient with myelodysplastic syndrome associated with isolated 5q deletion and JAK2 V617F mutation despite discontinuation of treatment

Hatzimichael

Lagos

Vassou

et al. 2016

Molecular and Clinical Oncology

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Abstract. Loss of a section of the long arm of chromosome 5, as a sole cytogenetic abnormality, characterizes a rare type of myelodysplastic syndrome [del(5q) MDS] and the co-existence of the JAK2 V617F mutation occurs in a small subset of these cases. Patients with isolated del(5q) MDS have a relatively favorable prognosis, with transformation to acute myeloid leukemia occurring in <10%, and their disease responds well to lenalidomide. However the optimal therapeutic approach for patients with del(5q) MDS in coexistence with the JAK2 V617F mutation, which is common to myeloproliferative neoplasms, remains to be elucidated. The present study reports a 77-year-old, transfusion-dependent female patient diagnosed with del(5q) MDS and a concomitant JAK2 V617F mutation. The patient was started on 10 mg lenalidomide daily for 21 days in a 28 day-cycle and within the first month of treatment, the patient became transfusion-independent. The only toxicity observed was grade 3 neutropenia, which was managed with transient treatment discontinuation and dose reduction on restart (5 mg). The patient achieved a complete cytogenetic and molecular response (normal karyotype and undetected JAK2 V617F mutation) within 6 months of treatment. However, 12 months post treatment initiation and while on hematological, cytogenetic and molecular response, the patient was unwilling to continue on treatment and lenalidomide was discontinued. The patient remains in hematological response, which lasts for >5 years despite treatment discontinuation. The present case highlights the coexistence of the JAK2 V617F mutation in del(5q) MDS and suggests that lenalidomide treatment is beneficial and effective for these patients, leading to complete hematological, cytogenetic and molecular response. Hematological response may be sustained for long periods of time, even following the discontinuation of the treatment.

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“…On the other hand, the JAK2V617F mutation has been found in only 6% of 97 patients with the 5q-syndrome, a myelodysplastic syndrome with isolated interstitial deletion of the long arm of chromosome 5(q31-q33), characterized by macrocytic anemia, variably elevated platelet count, hypolobated megakaryocytes in bone marrow biopsy, and a favorable course. 22 In this scanty group of patients, the presence of the V617F mutation correlated with higher platelet count.…”

Section: Causes Of Thrombocytosismentioning

confidence: 99%

Thrombocytosis and Thrombosis

Vannucchi¹,

Barbui²

2007

Hematology

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The aim of this review is to discuss current diagnostic approaches to, and classification of, patients presenting with thrombocytosis, in light of novel information derived from the discovery of specific molecular abnormalities in chronic myeloproliferative disorders (CMPD), which represent the most common cause of primary thrombocytosis. The JAK2V617F and the MPLW515L/K mutations have been found in patients with essential thrombocythemia, polycythemia vera, and primary myelofibrosis, and less frequently in other myeloproliferative disorders complicated by thrombocytosis. However, neither mutation is disease specific nor is it universally present in patients with elevated platelet counts due to a CMPD; therefore, distinguishing between reactive and primary forms of thrombocytosis, as well as among the different clinical entities that constitute the CMPD, still requires a multifaceted diagnostic approach that includes as a key step the accurate evaluation of bone marrow histology. The role of elevated platelet counts in thrombosis, which represent the predominant complication of CMPD,significantly affecting prognosis and quality of life as well as, paradoxically, in the pathogenesis of the hemorrhagic manifestations, will be discussed. Established and novel potential risk factors for thrombosis, including the clinical relevance of the JAK2V617F mutation, and current management strategies for thrombocytosis are also briefly discussed.

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The JAK2 V617F mutation identifies a subgroup of MDS patients with isolated deletion 5q and a proliferative bone marrow

Abstract: References1 Yang E, Korsmeyer SJ. Molecular thanatopsis: a discourse on the Bcl2 family and cell death.

Cited by 89 publications

References 8 publications

The impact of cytomorphology, cytogenetics, molecular genetics, and immunophenotyping in a comprehensive diagnostic workup of myelodysplastic syndromes

The impact of cytomorphology, cytogenetics, molecular genetics, and immunophenotyping in a comprehensive diagnostic workup of myelodysplastic syndromes

Durable response to lenalidomide in a patient with myelodysplastic syndrome associated with isolated 5q deletion and JAK2 V617F mutation despite discontinuation of treatment

Thrombocytosis and Thrombosis

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