RESUMEN
Background: Chronic myelomonocytic leukemia is a clonal hematological disorder with an inherent risk of transformation to acute myeloid leukemia. Recently, there has been exponential discovery of molecular abnormalities in patients with chronic myelomonocytic leukemia. Some of these mutations independently contribute to a higher risk of transformation and result in inferior overall survival. Treatment strategies for patients undergoing blastic transformation in chronic myelomonocytic leukemia, especially after progressing on hypomethylating agents, are currently limited.Case presentation: We present a case of a 70-year-old male patient with chronic myelomonocytic leukemia blastic transformation with RUNX1 mutation following azacitidine monotherapy. Notably, he achieved hematological complete remission after the first course of venetoclax plus azacitidine, leading to the disappearance of RUNX1 mutation. We performed serial assessments of molecular analysis by next generation sequencing throughout his clinical course.Conclusion: The presence of RUNX1 mutation is associated with higher response rates to venetoclax-based combination therapies in chronic myelomonocytic leukemia with blastic transformation. Our findings suggest that even after azacitidine monotherapy, venetoclax plus azacitidine is effective in targeting leukemic clones harboring RUNX1 mutations. Furthermore, we emphasize the significance of molecular analysis, including next-generation sequencing, in providing insights into the detailed dynamics of clonal evolution and guiding treatment decisions.
Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Leucemia Mielomonocítica Crónica , Mutación , Sulfonamidas , Humanos , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Masculino , Anciano , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Azacitidina/uso terapéutico , Azacitidina/administración & dosificación , Antineoplásicos/uso terapéuticoRESUMEN
Thrombosis in myeloproliferative neoplasms (MPNs) is an important clinical problem, and risk-stratified management is essential. To identify the clinical characteristics of thrombosis in patients with MPNs, a nationwide multi-institutional retrospective analysis (JSH-MPN-R18) was conducted. The aim of the present study was to perform a sub-analysis of JSH-MPN-R18 findings to clarify the predictive parameters for thrombosis among complete blood count (CBC) results. Among the patients enrolled in JSH-MPN-R18, those with essential thrombocythemia (ET; n = 1152) and polycythemia vera (PV; n = 456) were investigated. We analyzed and compared CBC parameters between patients with and those without any thrombotic events using Welch's T-test. Statistical analyses were performed using the R statistical software. Thrombotic events were observed in 74 patients with ET. In multivariate analysis, only the neutrophil ratio was slightly but significantly higher for ET patients with thrombosis than for those without (p < 0.05). Of note, the absolute neutrophil count (aNeu) was considered a useful predictive tool for thrombosis among patients classified as low-risk according to the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia. Among PV patients, those with thrombosis showed significantly higher hematocrit and aNeu than did those without thrombosis. As a thrombosis-associated factor, the neutrophil ratio was slightly but significantly elevated in patients with ET. This myeloid skew might reflect a higher value of JAK2 V617F allelic frequency in patients with ET with thrombosis; this was not clarified in JSH-MPN-R18. Further accumulation of evidence, including genetic information for JAK2 and other passenger mutations, is warranted.
Asunto(s)
Janus Quinasa 2 , Neutrófilos , Policitemia Vera , Trombocitemia Esencial , Trombosis , Humanos , Trombosis/etiología , Trombosis/sangre , Femenino , Masculino , Persona de Mediana Edad , Janus Quinasa 2/genética , Anciano , Estudios Retrospectivos , Trombocitemia Esencial/sangre , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/genética , Policitemia Vera/sangre , Policitemia Vera/complicaciones , Policitemia Vera/genética , Adulto , Trastornos Mieloproliferativos/sangre , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/genética , Recuento de Leucocitos , Valor Predictivo de las Pruebas , Anciano de 80 o más AñosRESUMEN
Many novel agents have been developed for BCR::ABL1-negaive myeloproliferative neoplasms (MPN), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Some of these agents not only achieve hematologic complete response, reduce spleen size, and alleviate constitutional symptoms, but also induce molecular response, which means that they reduce the allele burden of driver gene mutations. These agents also prevent and alleviate fibrosis in bone marrow, which reduces the incidence of thrombotic events and disease progression and might improve prognosis. This article discusses the latest findings and promising treatments, including ongoing clinical trials, in PV, ET, and PMF.
Asunto(s)
Trastornos Mieloproliferativos , Humanos , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/terapia , Trastornos Mieloproliferativos/diagnóstico , Mutación , Terapia Molecular DirigidaRESUMEN
A 47-year-old woman presented with subcutaneous hemorrhage. Blood tests revealed leukoerythroblastosis, anemia, and thrombocytopenia. Bone marrow biopsy led to a diagnosis of primary myelofibrosis (aaDIPSS, DIPSS-plus: intermediate-II risk). JAK2, CALR, and MPL mutations were not detected in peripheral blood, but targeted sequencing of bone marrow specimens revealed a double mutation (Q157R, S34F) in U2AF1. Allo-PBSCT was performed using an HLA-matched related donor, and post-transplantation bone marrow examination showed complete donor chimerism on day 55. Two years after allogeneic transplantation, the patient remains relapse-free. Although U2AF1 gene abnormality is known as a poor prognostic factor in primary myelofibrosis, this patient had a favorable long-term prognosis due to prompt transplantation therapy. This case highlights the importance of detailed gene mutation analysis in patients with triple-negative MF.
Asunto(s)
Mielofibrosis Primaria , Femenino , Humanos , Persona de Mediana Edad , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/terapia , Mielofibrosis Primaria/diagnóstico , Factor de Empalme U2AF/genética , Mutación , Médula Ósea/patología , Trasplante Homólogo , Janus Quinasa 2/genética , Calreticulina/genéticaRESUMEN
Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPN) in children, adolescents, and young adults (AYA) attract attention from hematologists because they are identified more than before due to the recognition and advancement of diagnostic capacity for Ph- MPN. The clinical features of Ph- MPN diagnosed in children and AYA are found to be different from those of Ph- MPN that occur in patients in their 60s, peak age of onset. Ph- MPN diagnosed in children and AYA has more triple-negative cases with no identifiable driver genes and a larger proportion of venous thrombosis in thrombotic events. In terms of treatment, there are still problems to be resolved that are unique to younger patients, such as choosing cytoreductive agents for long-term use and the development of optimal prevention of thrombotic or bleeding events during pregnancy and childbirth. In this paper, we will discuss the clinical research supporting these claims and offer some practical advice for treating young children with Ph- MPN daily.
Asunto(s)
Trastornos Mieloproliferativos , Neoplasias , Trombosis , Trombosis de la Vena , Embarazo , Femenino , Humanos , Adulto Joven , Adolescente , Niño , Preescolar , Cromosoma Filadelfia , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/terapia , Trombosis/etiología , Neoplasias/complicacionesRESUMEN
Acute hemolytic transfusion reaction (AHTR) is a rare but life-threatening complication of transfusion. We herein report a case of anti-Jkb IgM-related AHTR. Two hours after an 80-year-old man with myelodysplastic syndrome received a packed red blood cell (RBC) A+/Rh-/Jkb+/c- transfusion, he developed acute respiratory failure and a fever. Although he had tested negative in routine screening tests, the 37 °C normal saline test was weakly positive for Jkb. We confirmed the presence of anti-Jkb IgM in the patient's serum by flow cytometry. This case demonstrates the potential utility of flow cytometry for IgM detection.
RESUMEN
BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a disease entity with nonorganized granular glomerular deposition with monoclonal proteins of both heavy and light chains. Dysproteinemia was observed in only 30% of the patients with PGNMID. We herein report a case of PGNMID with discrepancy between serum and glomerular deposits. CASE PRESENTATION: The patient was a 50-year-old man who had been followed at a local clinic due to hypertension, type 2 diabetes, hyperlipidemia, hyperuricemia, fatty liver, and obesity. Proteinuria had been noted five years previously, and he had been referred to a hematology department due to hyperproteinemia, high gamma globulin, and κ Bence-Jones protein (BJP) positivity one year previously. Bone marrow aspiration showed 5% plasma cells, and he was referred to the nephrology department to evaluate persistent proteinuria. He was hypertensive, and his estimated glomerular filtration rate was 54.2 ml/min/1.73 m2. His urinary protein level was 0.84 g/gâ Cr. Urine and serum immunofixation showed BJP-κ type and IgG-κ type, respectively. Kidney biopsy showed an increase in mesangial cells and matrix without nodular lesions under a light microscope. Immunofluorescence microscopy showed granular deposits of IgG and C3 on the capillary wall and weak positivity for C1q. IgG3 was predominant among the IgG subclasses, and intraglomerular κ and λ staining was negative for κ and positive for λ. Direct fast scarlet staining was negative. Electron microscopy showed lumpy deposits without a fibrillar structure in the subepithelial area. Based on the above findings, a diagnosis of membranous nephropathy-type PGNMID was made. Since proteinuria increased gradually after three years of treatment with valsartan (40 mg, daily), oral prednisolone (30 mg, daily) was initiated, which led to decreased proteinuria. The dose of oral prednisolone was gradually tapered to 10 mg per day. At that time, proteinuria was 0.88 g/gâ Cr. We found 204 cases in 81 articles in the PubMed database, among which 8 showed discrepancy in the heavy and/or light chains between serum and kidney. CONCLUSIONS: We experienced a case of membranous nephropathy-type PGNMID with discrepancy in light chains between serum and kidney that was successfully treated with oral prednisolone.
Asunto(s)
Diabetes Mellitus Tipo 2 , Glomerulonefritis Membranosa , Glomerulonefritis , Hipertensión , Enfermedades Renales , Masculino , Humanos , Persona de Mediana Edad , Inmunoglobulina G , Glomerulonefritis/diagnóstico , Glomerulonefritis/tratamiento farmacológico , Proteinuria , Anticuerpos MonoclonalesRESUMEN
OBJECTIVES: This Japanese cross-sectional survey evaluated the symptoms, daily living activities, and treatment needs of patients with polycythemia vera (PV), as perceived by patients themselves and their physicians. METHODS: The study was conducted at 112 centers (March to July 2022) and included PV patients aged ≥20 years (n = 265) and their attending physicians (n = 151). The patient and physician questionnaires included 34 and 29 questions, respectively, to assess daily living, PV symptoms, treatment goals, and physician-patient communication. RESULTS: Concerning daily living (primary endpoint), work (13.2%), leisure activities (11.3%), and family life (9.6%) were most affected by PV symptoms. Patients aged <60 years more frequently reported an impact on daily living than patients aged ≥60 years. Some patients (30%) reported anxiety about their future condition. The most common symptoms were pruritus (13.6%) and fatigue (10.9%). Pruritus was ranked as the first treatment need for patients, while physicians ranked it fourth. Concerning treatment goals, physicians prioritized thrombosis/vascular event prevention, while patients prioritized delaying PV progression. Physicians were less satisfied with physician-patient communication than patients. CONCLUSIONS: Patients' daily living was largely affected by PV symptoms. There are differences in physician and patient perceptions of symptoms, daily living, and treatment needs in Japan. TRIAL REGISTRATION: UMIN Japan identifier: UMIN000047047.
Asunto(s)
Médicos , Policitemia Vera , Humanos , Estudios Transversales , Japón/epidemiología , Policitemia Vera/terapia , PruritoRESUMEN
A 44-year-old woman presented with severe anemia. We strongly suspected gastrointestinal bleeding; however, esophagogastroduodenoscopy, colonoscopy, and computed tomography showed no bleeding sources. Video capsule endoscopy revealed an actively bleeding submucosal lesion within the jejunum. Double-balloon enteroscopy revealed a 20-mm continuously bleeding submucosal lesion in the distal jejunum. We suspected small intestinal vascular malformation and performed surgical resection. The resected specimen pathologically comprised dilated, thin-walled lymphatic channels and blood vessels involving the small intestinal submucosa. Therefore, the patient was diagnosed with small intestinal lymphatic-venous malformation. Postoperatively, the patient recovered well, and recurrence was not observed.
Asunto(s)
Intestino Delgado , Malformaciones Vasculares , Femenino , Humanos , Adulto , Intestino Delgado/diagnóstico por imagen , Intestino Delgado/cirugía , Intestino Delgado/irrigación sanguínea , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/cirugía , Hemorragia Gastrointestinal/diagnóstico , Yeyuno/diagnóstico por imagen , Yeyuno/cirugía , Colonoscopía/efectos adversos , Malformaciones Vasculares/complicacionesRESUMEN
BACKGROUND: Improper prescriptions can cause adverse reactions in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: Hospital pharmacists investigated improper prescriptions, prerenal acute kidney injury (AKI) prescriptions, and adverse effects in AKI in 199 CKD patients at Kouseikai Hospital from July 2020 to June 2021, as well as combinations of "triple whammy" drugs (renin-angiotensin-system inhibitors, diuretics, and non-steroidal anti-inflammatory drugs) plus active vitamin D preparations. All participants (average age, 73.6 ± 16.2 years) were residents of Nagasaki City or its suburbs. RESULTS: Adverse reactions occurred in 38 of the 199 patients (19.1%). 13 patients had AKI, and 9 of these cases developed during the summer. A comparison of the 38 patients in the adverse reaction group and the 161 patients in the non-occurrence group showed that the former group was significantly older and had a lower body weight. In terms of renal function, estimated glomerular filtration rate (mL/min/1.73m2) was significantly lower, blood urea nitrogen/serum creatinine (BUN/S-Cr) was higher, dehydration was involved, and active vitamin D preparations were significantly more common in the adverse reaction group. CONCLUSION: Our findings suggest that concomitant prescription of active vitamin D in combination with the drugs that constitute the triple whammy should be avoided. The absence of hypercalcemia should be confirmed and adequate fluid intake should be encouraged to prevent prerenal nephropathy.
Asunto(s)
Lesión Renal Aguda , Insuficiencia Renal Crónica , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Vitamina D/efectos adversos , Antagonistas de Receptores de Angiotensina/efectos adversos , Combinación de Medicamentos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/inducido químicamente , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/complicacionesRESUMEN
Hematopoiesis was considered a hierarchical stepwise process but was revised to a continuous process following single-cell RNA sequencing. However, the uncertainty or fluctuation of single-cell transcriptome dynamics during differentiation was not considered, and the dendritic cell (DC) pathway in the lymphoid context remains unclear. Here, we identify human B-plasmacytoid DC (pDC) bifurcation as large fluctuating transcriptome dynamics in the putative B/NK progenitor region by dry and wet methods. By converting splicing kinetics into diffusion dynamics in a deep generative model, our original computational methodology reveals strong fluctuation at B/pDC bifurcation in IL-7Rα+ regions, and LFA-1 fluctuates positively in the pDC direction at the bifurcation. These expectancies are validated by the presence of B/pDC progenitors in the IL-7Rα+ fraction and preferential expression of LFA-1 in pDC-biased progenitors with a niche-like culture system. We provide a model of fluctuation-based differentiation, which reconciles continuous and discrete models and is applicable to other developmental systems.
Asunto(s)
Diferenciación Celular , Células Dendríticas , Antígeno-1 Asociado a Función de Linfocito , Diferenciación Celular/genética , Células Dendríticas/metabolismo , Hematopoyesis , Humanos , Antígeno-1 Asociado a Función de Linfocito/genética , Antígeno-1 Asociado a Función de Linfocito/metabolismo , Transcriptoma/genéticaRESUMEN
The presence of a JAK2 V617F or JAK2 exon 12 mutation is one of the three major criteria listed for the diagnosis of polycythemia vera (PV) in the 2017 World Health Organization Classification. However, a nationwide study has not yet been conducted in Japan since the discovery of JAK2 mutations. Therefore, the Japanese Society of Hematology (JSH) retrospectively analyzed the clinical characteristics of 596 Japanese patients with PV diagnosed between April 2005 and March 2018. Among the 473 patients with complete data on JAK2 mutations available, 446 (94.3%) and 10 (2.1%) were positive for the JAK2 V617F and JAK2 exon 12 mutations, respectively. During a median follow-up of 46 months (range: 0-179 months), 47 (7.9%) deaths occurred. The major causes of death were secondary malignancies (23.4%), acute leukemia (12.8%), non-leukemic progressive disease (10.6%) and thrombotic (6.4%) and hemorrhagic complications (6.4%). Thrombotic and hemorrhagic events occurred during the clinical course in 4.0% (n = 24) and 3.5% (n = 21) of patients, respectively. These results show that the international PV prognostic score (age, venous thrombosis and leukocytosis) is applicable to Japanese patients with PV.
Asunto(s)
Hematología , Policitemia Vera , Trombosis , Humanos , Policitemia Vera/complicaciones , Japón/epidemiología , Janus Quinasa 2/genética , Estudios Retrospectivos , Trombosis/etiología , MutaciónRESUMEN
We conducted a large-scale, nationwide retrospective study of Japanese patients who were diagnosed with essential thrombocythemia based on the diagnostic criteria in the World Health Organization classification. We investigated clinical characteristics, survival rates, and the incidence of thrombohemorrhagic events as well as risk factors for these events. A total of 1152 patients were analyzed in the present study. Median age at diagnosis was 65 years, the median platelet count was 832 × 109/L, and the positive mutation rates of JAK2V617F, CALR, and MPL were 62.8, 25.1, and 4.1%, respectively. Compared with European and American patients, Japanese patients were more likely to have cardiovascular risk factors and less likely to have systemic symptoms including palpable splenomegaly. Thrombocytosis was identified as a risk factor for hemorrhagic events and prognosis, but not for thrombotic events. The prognostic factors and risk classifications reported in Europe and the United States were generally applicable to Japanese patients. Regarding transformations, secondary myelofibrosis progressed in a time-dependent manner, but progression to acute leukemia was low in "true" ET patients. Skin cancers were less common and gastrointestinal cancers more common as secondary malignancies in Japanese patients, suggesting ethnic differences.
Asunto(s)
Trombocitemia Esencial/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/epidemiología , Adulto JovenRESUMEN
Essential thrombocythemia (ET) and polycythemia vera (PV) are myeloproliferative neoplasms (MPN), wherein JAK2 V617F mutation exists as a common driver mutation, and the JAK-STAT pathway is constitutively activated. The treatment goal for ET and PV is the prevention of thrombosis and bleeding. The treatment strategy for ET is careful observation or antiplatelet therapy with or without cytoreductive therapy based on the thrombotic risk. The treatment strategy for all PV patients is phlebotomy with a target hematocrit of <45% in addition to antiplatelet therapy. Moreover, for patients at a high risk of thrombosis, additional cytoreductive therapy is considered beneficial. In this session, we discuss important points for ET diagnosis, thrombotic risk stratification, and the details of treatment strategy and current practice with evidence from clinical trials in ET. Furthermore, current topics in the treatment of ET and PV will be introduced with a focus on clinical data about interferon-α, which is reported to induce not only hematologic response but also molecular and histopathologic response in MPN.
Asunto(s)
Trastornos Mieloproliferativos , Policitemia Vera , Trombocitemia Esencial , Trombosis , Hemorragia , Humanos , Janus Quinasa 2/genética , Policitemia Vera/diagnóstico , Policitemia Vera/terapia , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/genética , Trombocitemia Esencial/terapia , Trombosis/etiología , Trombosis/prevención & controlRESUMEN
Antifungal prophylaxis is crucial for successful hematopoietic stem cell transplantation (HSCT). Maintenance therapy with fluconazole (FLCZ) is generally prescribed as secondary prophylaxis in patients with human immunodeficiency virus infection and non-immunocompromised hosts. However, previous reports have revealed that FLCZ is insufficient as a secondary prophylaxis for cryptococcal infection in HSCT cases. There is no well-established evidence of effective secondary prophylaxis against cryptococcal infection in conditions of severe immunosuppression, such as in HSCT. Herein, we report a case of atypical chronic myeloid leukemia (aCML) presenting with cryptococcal meningitis. A 58-year-old man with progressive leukocytosis and headache was referred to our hospital. Bone marrow biopsy revealed aCML. Because the estimated overall survival was limited, HSCT was indicated. Furthermore, enhanced magnetic resonance imaging and lumbar puncture aided in diagnosing cryptococcal meningitis, which was treated with a combination therapy comprising liposomal amphotericin B and 5-fluorocystine for 28 days. Given the high recurrence rate of cryptococcal meningitis, voriconazole (VRCZ) dose was calculated using the trough concentration of VRCZ in the cerebrospinal fluid. Eventually, HSCT was successfully performed at an appropriate therapeutic range of VRCZ. To the best of our knowledge, there is no case report on HSCT with secondary prophylaxis against cryptococcal meningitis. Our report thus emphasizes the efficacy of VRCZ maintenance therapy as secondary prophylaxis for cryptococcal infection.
Asunto(s)
Cadenas Ligeras de Inmunoglobulina/metabolismo , Enfermedades Renales/diagnóstico , Enfermedades Renales/etiología , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Gammopatía Monoclonal de Relevancia Indeterminada/complicaciones , Anciano de 80 o más Años , Biomarcadores , Biopsia , Femenino , Humanos , Túbulos Renales Proximales/ultraestructura , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Evaluación de SíntomasRESUMEN
Immunotactoid glomerulopathy (ITG) is characterized by Congo red-negative microtubular deposits, and it has been reported as a rare paraneoplastic syndrome due to hematologic malignancies, viral infections, or autoimmune diseases. In hematologic malignancies, multiple myeloma and other mature B-cell malignancies are the most common hematologic malignancies, and Hodgkin lymphoma (HL) is extremely rare. A 59-year-old woman was admitted to our hospital because of a pulmonary mass and proteinuria. Computed tomography-guided lung biopsy confirmed the presence of HL stage IIA. Immunofixation of peripheral blood was positive for immunoglobulin G (IgG) kappa. Renal biopsy showed mesangial proliferation with deposits in the subendothelial lesion and no invasion of the HL. These deposits were positive for IgG3, C3, and kappa light chain but negative for C1q and lambda light chain. Electron microscopy showed randomly aligned tubular structures with a diameter of approximately 50 nm. We diagnosed the patient with immunotactoid nephropathy and HL. After systemic chemotherapy, the patient achieved a complete response and loss of proteinuria. On the contrary, her serum monoclonal gammopathy was observed after chemotherapy. The existence of a monoclonal antibody itself might not be a sufficient factor for ITG in some cases, and an additive trigger is necessary for development.
RESUMEN
MPL exon 10 mutations are one of the driver mutations in essential thrombocythemia (ET) or myelofibrosis (MF). We have established an in-house MPL mutation analysis system, covering the entire region of MPL exon 10 by direct sequencing. Since 2009, MPL exon 10 mutation analysis has been performed for diagnosis of myeloproliferative neoplasms (MPN) without JAK2 V617F or CALR exon 9 mutations. So far, 11 cases of MPL exon 10 mutation have been found in 51 patients with suspected MPN. In patients with ET, we detected five non-canonical MPL mutations including one novel mutation, MPL R514_P518delinsK, and one canonical MPL W515L mutation. Notably, three ET patients without canonical MPL mutations had thrombotic events. Meanwhile, in primary or secondary MF, only canonical MPL W515L/K mutations were found. Further cases need to be examined to elucidate the full MPL mutation profile in MPN. However, our data indicate that analysis of the whole of MPL exon 10 is warranted for the diagnosis of MPL mutations, especially in ET, and that the use of Japanese commercial laboratory tests that only detect canonical MPL W515L/K mutations may miss a significant percentage of MPL exon 10 mutations, which could delay the administration of anti-thrombotic therapy.