Clinical characteristics, prognostic factors, and outcomes of patients with essential thrombocythemia in Japan: the JSH-MPN-R18 study

Hashimoto, Yoshinori; Ito, Tomoki; Gotoh, Akihiko; Nakamae, Mika; Kimura, Fumihiko; Koike, Michiaki; Kirito, Keita; Wada, Hideho; Usuki, Kensuke; Tanaka, Takayuki; Mori, Takehiko; Wakita, Satoshi; Saito, Toshiki; Kada, Akiko; Saito, Akiko; Shimoda, Kazuya; Sugimoto, Yuka; Kurokawa, Toshiro; Tomita, Akihiro; Edahiro, Yoko; Akashi, Koichi; Matsumura, Itaru; Takenaka, Katsuto; Komatsu, Norio

doi:10.1007/s12185-021-03253-0

Cited by 12 publications

(13 citation statements)

References 48 publications

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“…These characteristics are comparable to those in a previous report. 9,13 However, events such as cerebral infarction in the father of a patient that in a large number of patients with TN ET, the frequency of thrombotic events was higher than in patients with the JAK2 V617F mutation or those with the CALR mutation. 26 delayed, which may influence therapeutic intervention.…”

Section: Discussionmentioning

confidence: 96%

“…This frequency is comparable to that in previous studies. 7,13 Using WES and target sequencing, we identified putative driver mutations in 7 of 20 (35.0%) triple-negative ET cases. Among the seven cases, there were four (20% of TN ET cases) with germline mutations (JAK2 T875N, THPO splicing site mutation [NM_001290022.1: c.559 The clinical characteristics of TN ET cases were younger age (vs. JAK2 mutation), lower white blood cell counts (vs. JAK2 mutation), and lower LDH values (vs. JAK2 or CALR mutations) (Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…ET cases without canonical JAK2, CALR, or MPL mutations, that is, triple-negative (TN) ET, have been found in 10%-20% of ET cases. 7,13 Due to the limited number of cases, its clinical significance remains largely unclear. However, reported features include fewer male individuals, lower platelet counts, lower lactate dehydrogenase (LDH) levels, and less splenomegaly.…”

Section: Introductionmentioning

confidence: 99%

“…5 Regarding thrombotic complications, some studies report less thrombosis in TN ET cases, 5 while others report no difference between the types of mutations. 13 The risk of thrombosis in TN ET is inconclusive owing to the small number of cases and limited thrombotic events. These may vary depending on the type of noncanonical driver mutation.…”

Section: Introductionmentioning

confidence: 99%

“…ET cases without canonical JAK2 , CALR , or MPL mutations, that is, triple‐negative (TN) ET, have been found in 10%–20% of ET cases 7,13 . Due to the limited number of cases, its clinical significance remains largely unclear.…”

Section: Introductionmentioning

confidence: 99%

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Identification of putative noncanonical driver mutations in patients with essential thrombocythemia

Arai

Yoshimitsu

Otsuka

et al. 2023

European J of Haematology

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Essential thrombocythemia (ET) cases without canonical JAK2, CALR, or MPL mutations, that is, triple‐negative (TN) ET, have been found in 10%–20% of ET cases. Owing to the limited number of TN ET cases, its clinical significance remains unclear. This study evaluated TN ET's clinical characteristics and identified novel driver mutations. Among 119 patients with ET, 20 (16.8%) had no canonical JAK2/CALR/MPL mutations. Patients with TN ET tended to be younger and had lower white blood cell counts and lactate dehydrogenase values. We identified putative driver mutations in 7 (35%): MPL S204P, MPL L265F, JAK2 R683G, and JAK2 T875N were previously reported as candidate driver mutations in ET. Moreover, we identified a THPO splicing site mutation, MPL*636Wext*12, and MPL E237K. Four of the seven identified driver mutations were germline. Functional studies on MPL*636Wext*12 and MPL E237K revealed that they are gain‐of‐function mutants that increase MPL signaling and confer thrombopoietin hypersensitivity with very low efficiency. Patients with TN ET tended to be younger, although this was thought to be due to the inclusion of germline mutations, hereditary thrombocytosis. Accumulating the genetic and clinical characteristics of noncanonical mutations may help future clinical interventions in TN ET and hereditary thrombocytosis.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%