Volume 103 · Issue 45 · 2023

Classical myeloproliferative neoplasms (MPN), also known as Ph^-MPN, includes polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Secondary myelofibrosis (sMF) and secondary acute myeloid leukemia (sAML) are important disease progressions of MPN. After MPN disease progression, hematopoietic stem cells undergo new clonal evolution, leading to drug resistance, poor treatment effect and poor survival of patients. In recent years, the exploration of the mechanism of disease progression and the precise diagnosis and treatment of MPN have attracted much attention. This article summarizes the research status of MPN disease progression, including the pathogenesis, risk stratification, and precision treatment, in order to provide reference for exploring new diagnosis and treatment methods of MPN disease progression.

The mutations of myeloproliferative neoplasma (MPN) mainly include driver mutations and non-driver mutations. The driver mutations mainly include JAK2 mutations, CALR mutations and MPL mutations and non-driver mutations mainly include ASXL1, DNMT3A, TET2, SF3B1, EZH2, TP53, SRSF2, USAF1, etc. Driver and non-driver mutations and their clonal evolution affect the thrombosis and disease transformation of MPN. Clonal hematopoiesis of MPN can occur decades before diagnosis, even in the fetal stage. After the emergence of clonal hematopoiesis, until the emergence and progression of MPN, gene mutation order, inflammation, interferon therapy affect the disease phenotype and clonal hematopoiesis of MPN. Although great progress has been made in the understanding of MPN clonal hematopoiesis and its evolution with the development of next-generation sequencing, there are still many limitations. In this study, we mainly discuss gene mutations of MPN and their influences on the thrombosis, leukemia and fibrosis transformation, and the influencing factors of clonal evolution, aiming to summarize the influence of clonal hematopoiesis and its evolution on the complications, prognosis and survival of MPN.

Alzheimer′s disease (AD) is known as the most prevalent type of dementia in the elderly population. However, AD is regarded as a persistent sever clinical challenge due to its high morbidity but low rates of diagnosis and treatment in China. Intracerebral β-Amyloid protein deposition is the earliest pathological process that occurs in the continuous spectrum of AD, prior to clinical symptoms such as cognitive decline. Standardizing the operation and result interpretation of amyloid positron emission tomography (PET) during the clinical practice, and achieving the reliability, repeatability and comparability of the imaging process and results will contribute to the early and accurate diagnosis, efficacy evaluation, and outcome prediction. A global binary interpretation (positive or negative) of amyloid PET images is recommended. In clinical interpretation, amyloid PET image results should be combined with clinical and neuropsychological characteristics, other morphological and/or functional imaging data, and other biological markers.

Wound irrigation is one of the most effective means to prevent open wound infection after injury. Wound irrigation can reduce the risk of wound infection and promote wound healing by removing the cell fragments, surface bacteria, dressings residues, residual foreign body and wound exudates loosely attached to the wound. The effect of wound irrigation mainly depends on the pressure of irrigation, the direction of fluid flow, the type of liquid, temperature and volume/amount of irrigation fluid. In response to the phenomenon that emergency open wounds are not irrigated in a standardized manner in China, the Posttraumatic Special Infections and Biting Injury Study Group of the Trauma Surgeons Branch of the Chinese Medical Doctor Association and the Animal Injury Treatment Branch of China Association for Disaster and Emergency Rescue Medicine organized domestic experts in the fields of emergency department and trauma treatment centers to collect the latest clinical evidence of emergency open wound irrigation, and wrote this consensus with reference to relevant guidelines, consensus and the clinical experience of Chinese experts. The consensus summarized the important factors affecting wound irrigation and put forward 10 recommendations to improve the knowledge and skills of trauma emergency medical personnel in wound irrigation.

Postoperative delirium of cardiovascular surgery occurs in up to 26%-52% of patients after cardiovascular surgery and is associated with adverse outcomes, including increased hospital length of stay, higher cost of care, higher rates of readmission. The combination of multiple factors leads to postoperative delirium of cardiovascular surgery, including preoperative (previous psychiatric conditions and cognitive disfunction, cerebrovascular disease, age, cardiac insufficiency, and so on), intraoperative (duration of surgery>5 h, emergency surgery, anesthetic drugs, direct myocardial injury, and so on) and postoperative (pain, sleep disturbance, Deep sedation, duration of mechanical ventilation>72 h) risk factors. On the basis of the latest literature at home and abroad and the clinical experience of many experts, the Cardiac Critical Care Branch of China International Exchange and Promotive Association for Medical and Health sought to develop a consensus document"Chinese expert consensus on the prevention and treatment of postoperative delirium of cardiovascular surgery", in order to standardize the management of postoperative delirium of cardiovascular surgery and improve the prognosis of patients.

To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG-IFN-α2b) in the treatment of myeloproliferative neoplasm (MPN).

Thirty-four MPN patients receiving PEG-IFN-α2b treatment in the Second Hospital of Tianjin Medical University from August 2019 to October 2022 were prospectively included. Among the patients, 9 were male and 25 were female, and the median age [M (Q₁, Q₃)] was 57 (19, 78) years. Patients′ clinical characteristics were collected and the follow-up was performed. As of January 30, 2023, the follow-up period [M(Q₁, Q₃)] was 24 (16, 33) months. The efficacy, safety and changes in immune cell and cytokine levels after 12 and 24 months of treatment were analyzed.

During the follow-up period, 4 patients dropped out, and the efficacy was evaluable in 30 patients. Following 12 and 24 months of treatment, the complete hematologic response (CHR) rates were 57.1% (16/28) and 75.0% (18/24), respectively. The complete molecular response (CMR)+partial molecular response (PMR) rates were 27.3% (6/22) and 55.0% (11/20), respectively. The bone marrow histopathological overall response rates (ORR) were 34.6% (9/26) and 47.6% (10/21), respectively. At 12 and 24 months of treatment, the proportions of CD8⁺HLA-DR⁺T cells, effector T cell subpopulations, CD56^bright natural killer (NK) cells, and plasmacytoid dendritic cells (pDC) were higher than the pre-treatment levels, while the proportion of CD56^dim NK cells was lower than the pre-treatment level (all P<0.05). The levels of motif chemokine ligand 10 (CXCL10), tumor necrosis factor (TNF)-α and TNF-β in bone marrow all increased from those prior to treatment, while the levels of vascular endothelial growth factor (VEGF) and interleukin (IL-4) decreased from those prior to treatment (all P<0.05). Among hematological adverse reactions, white blood cells decrease [47% (16/34)] was observed with high incidence. Among non-hematological adverse reactions, asthenia [44.1% (15/34)] and transaminases increase [32.3% (11/34)] were observed with high incidences.

PEG-IFN-α2b has high hematologic, molecular, and bone marrow histopathological response rates in the treatment of MPN. It can reduce malignant clone loads and regulate the immune microenvironment and is safe and well tolerated overall.

To analyze the risk factors of thrombosis in patients with JAK2^V617F mutation positive myeloproliferative neoplasms (MPN).

A total of 223 MPN patients with JAK2^V617F mutation in the Second Hospital of Tianjin Medical University from September 2017 to May 2023 were retrospectively enrolled, including 111 males and 112 females, aged [M(Q₁,Q₃)] 57(21,66) years. According to the presence or absence of thromboembolism during follow-up, the patients were divided into thrombosis group (n=102) and non-thrombosis group (n=121). The clinical characteristics, laboratory characteristics, cytogenetics and other disease progression and survival of the two groups of patients were analyzed. As of March 31, 2023, the follow-up period [M (Q₁, Q₃)] was 6 (3, 10) years. The influencing factors of thrombosis in JAK2^V617F positive MPN patients were analyzed by using the Cox risk model.

Among 223 JAK2^V617F positive MPN patients, 144 were polycythemia vera (PV), 51 were essential thrombocythemia (ET) and 28 were primary myelofibrosis (PMF). The mutation rates of ASXL1 and BCORL1 genes in the thrombosis group were 19.6% (20/102) and 6.9% (7/102), respectively, which were higher than those in the non-thrombosis group [9.1% (11/121) and 0.8% (1/121)] (both P<0.05). The proportion of monocytes, C-reactive protein (CRP), interleukin-1β (IL)-1β, IL-8 and tumor necrosis factor-β (TNF-β) increased in the thrombosis group were higher than those in the non-thrombosis group (all P<0.05). Multivariate analysis showed that age≥60 years (HR=2.132, 95%CI: 1.376-3.303, P=0.001), history of thrombosis (HR=3.636, 95%CI: 2.121-6.202, P<0.001), ASXL1 mutation positive (HR=2.245, 95%CI: 1.093-3.231, P=0.022) and elevated TNF-β (HR=2.009, 95%CI: 1.113-3.624, P=0.021) were risk factors for thrombosis in JAK2^V617F positive MPN patients.

In addition to age, history of thrombosis and positive ASXL1 mutation, elevated TNF-β is also an influencing factor of thrombosis in JAK2^V617F positive MPN patients. Intervention of inflammation may have a certain effect on the prevention and treatment of thrombosis.

To investigate the expression level of WT1 gene in patients with classical Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPN) and its correlation with clinical features.

A retrospective study included 252 patients with newly diagnosed MPN in Zhongnan Hospital of Wuhan University from January 2015 to March 2023, including 128 males and 124 females, aged［M（Q₁，Q₃）］62 (53, 69) years. The WT1-positive group (n=93) and the WT1-negative group (n=159) were split based on the level of WT1 gene expression, and the variations in clinical indicators between the two groups were compared. Its levels of expression in each subtype and its relationships to thrombotic events and clinically significant variables were analyzed. As of March 31, 2023, the follow-up period [M (Q₁, Q₃)] was 12.0(6.5,21.0)months. The risk factors of thrombosis in MPN patients were analyzed by using the logistic regression analysis.

The WT1 gene expression level in the overall bone marrow samples of 252 patients with newly diagnosed MPN was 0.30% (0.10%, 1.10%). The expression level in primary myelofibrosis (PMF) patients was 1.45% (0.41%, 3.24%), which was higher than 0.15% (0.02%, 0.32%), 0.37% (0.16%, 1.09%) in essential thrombocythemia (ET) and polycythemia vera (PV) patients (both P<0.05). Positive correlations were found between WT1 gene expression levels and JAK2^V617F gene mutation load, RDW, MPV (r=0.478, 0.346, 0.236, all P<0.01). While negative correlations between WT1 gene expression levels and PLT, LYM, PTTA, LDH were found (r=-0.339, -0.170, -0.206, -0.388, all P<0.01). Patients in the WT1-positive group exhibited a higher percentage of somatic symptoms, splenomegaly, positive JAK2^V617F gene mutation, and higher levels of RDW, LDH, NEUT, and MPV compared to the WT1-negative group. In contrast, the proportion of triple-negative (negative for all three hot mutations of JAK2^V617F, CALR and MPL) was lower, and the levels of PLT, LYM and PTTA were lower (all P<0.05). The thrombotic event rates of WT1-positive group and WT1-negative group were 32.3% (30/93) and 32.1% (51/159), respectively, and the difference was not statistically significant (P=0.883). Logistic regression analysis showed that male (OR=2.41,95%CI:1.02-5.71,P=0.046) and positive JAK2^V617F gene mutation (OR=3.96,95%CI:1.50-10.42,P=0.005) were risk factors for thrombotic events in ET patients.

WT1 gene expression is elevated in PMF patients and correlated with indicators of disease progression and transformation in MPN patients. It can be utilized as an auxiliary diagnostic indicator for classical MPN staging but is not correlated with the incidence of thrombotic events. Male and positive JAK2^V617F gene mutation are risk factors for thrombotic events in ET patients.

To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of primary myelofibrosis (PMF) patients.

A total of 14 cases of PMF who underwent allo-HSCT from December 2008 to December 2022 were analyzed retrospectively, including 8 males and 6 females with a median age [M(Q₁, Q₃)]of 36 (24, 42) years. Three-year overall survival (OS), disease free survival (DFS), cumulative incidence of relapse (CIR), transplantation-related mortality (TRM) were analyzed. Meanwhile, the complications were followed up by telephone and outpatient appointments for 49.6 (9.0,93.1) months.

All patients received myeloablative conditioning regimens (MAC). All patients had successful engraftment, and the median time of neutrophils and platelet engraftment were 13.5 (11.8, 18.0) days and 19.5 (13.5, 24.5) days, respectively. Ⅱ-Ⅳ acute graft versus host disease (GVHD) occurred in 3 cases, while chronic GVHD in 8 cases. The rate of 3-year OS,DFS,CIR and TRM were (92.9±6.9)%, (76.0±12.2)%, (38.6±2.7)% and (7.1±0.5)% respectively after a median follow-up time of 1 489.0 (270.3,2 794.8) days. Two patients died from treatment-related complications, one of which died 39 days after transplantation due to heart failure caused by severe anemia, the other patient died 6 years after relapse due to pulmonary infection.

Allo-HSCT can be used as a safe and effective approach to treat PMF.

To explore the effect of early rehabilitation training on motor function and neural function of patients with brainstem hemorrhage after stereotactic individualized operation.

A total of 84 patients with brainstem hemorrhage after stereotactic individualized surgery admitted to Nanyang Central Hospital from January 2020 to January 2022 were selected as the study subjects.The patients were randomly divided into observation group (n=42) and control group (n=42) according to random number table method. The control group received conventional Western medicine treatment, and the observation group received early rehabilitation training on the basis of drug treatment in the control group. The motor function assessment [Fugl Meyer Assessment (FMA) scores], neural function [National Institutes of Health Stroke Scale (NIHSS) scores], ability of daily living [Barthel index (BI) scores], cerebral blood flow [mean blood flow (MBF), mean flow velocity (MFV), peripheral vascular resistance (PVR)] and nerve factor [serum neuron specific enolase (NSE), brain derived neurotrophic factor (BDNF), central nervous specific protein(S100β)] levels were compared between the two groups before and after the treatment. In addition, the rehabilitation effect and complications of the two groups were observed.

The total effective rate (95.24%) in the observation group was higher than that in the control group (76.19%%) (P<0.05). After the treatment, the FMA scores, BI scores, MBF, MFV and BDNF levels of the two groups were higher than those before the treatment, and the observation group were higher than the control group (P<0.05). NIHSS scores, PVR, NSE and S100β levels in the two groups after the treatment were lower than those before the treatment, and those in the observation group were lower than those in the control group (P<0.05). The incidence of complications in the observation group [7.14% (3/42)]was lower than that in the control group [23.81% (10/42), P<0.05].

For patients with brain stem hemorrhage after stereotactic individualized surgery, early rehabilitation training can improve the motor, neural function and daily living ability, rehabilitation effect, regulate cerebral hemodynamics and nerve factor levels, and reduce the incidence of complications.

To clarify the efficacy and safety of endoscopic submucosal dissection (ESD) with additional radiotherapy in T1a-MM/T1b-SM esophageal squamous cell carcinoma (ESCC).

A retrospective analysis was conducted on 71 patients with T1a-MM/T1b-SM ESCC admitted to Southeast University Affiliated Zhongda Hospital from January 2015 to December 2019. The patients were divided into two groups based on the treatment method: the ESD group (ESD therapy alone) and the ESD-radiotherapy group (ESD combined radiotherapy). The follow-up duration after ESD was (44±17) months. The difference of disease-free survival (DFS) rate and overall survival (OS) rate between the two groups was compared by survival analysis, and the occurrence of complications was compared. Baseline variables of the two groups were compared and the influencing factors of DFS rate were analyzed by Cox proportional risk regression model.

There were 44 patients in the ESD-radiotherapy group [28 males, 16 females, aged (65±7) years] and 27 patients in the ESD group [18 males, 9 females, aged (67±9) years]. The results of survival analysis show that the 1, 3 and 5-year DFS rates of ESD-radiotherapy group were 95.5%, 92.9% and 77.4%, respectively, which were higher than those of ESD group 85.2%, 73.2% and 62.7% (all P<0.05). The 1, 3 and 5-year OS rates of the ESD-radiotherapy group were 100%, 94.7% and 94.7%, while those of the ESD group were 96.3%, 96.3% and 79.4%, respectively. The difference was not statistically significant (all P>0.05). Cox proportional hazard regression model analysis showed that ESD combined with radiotherapy (HR=0.19, 95%CI: 0.04-0.90, P=0.037), complete tumor resection (HR=0.25, 95%CI: 0.07-0.86, P=0.027), and vascular invasion (HR=12.06, 95%CI: 1.61-90.26, P=0.015) were the influencing factors of DFS rates. The most common complication of ESD was esophageal stenosis, and no grade 3 or higher radiation adverse reactions occurred after combined radiotherapy.

ESD combined radiotherapy is an effective and safe therapeutic strategy for patients with T1a-MM/T1b-SM ESCC.

To systematically evaluate the effect of tumor spread through air spaces (STAS) on the prognosis of patients with stage Ⅰ non-small cell lung cancer (NSCLC).

PubMed, Embase, Web of Science, Cochrane Library, CNKI, Wanfang Database and VIP were searched to collect papers related to NSCLC and STAS published from the establishment of aboves databases to November 2022. Papers were screened according to the inclusion and exclusion criteria, and data were extracted. The 5-year overall survival (OS) and relapse-free survival (RFS) of stage Ⅰ NSCLC patients with or without STAS were compared. HR(95%CI) was used as effective indicator to evaluate the impact of STAS positivity on the prognosis of NSCLC. The quality of each included study was assessed using the Newcast-Ottawa Scale (NOS).

A total of 24 papers concerning 29 studies were included according to the inclusion and exclusion criteria, and there was no significant heterogeneity among the included papers(all I²<50%). A total of 10 883 patients with stage Ⅰ NSCLC were included in the studies, of which 3 298 (30.3%) were STAS-positive. The 29 studies showed that STAS-positive patients had a higher risk of 5-year recurrence than STAS-negative patients with stage Ⅰ NSCLC [HR=1.94(95%CI:1.74-2.16)];and a meta-analysis of 17 of the studies showed that that STAS-positive patients had a higher risk of 5-year death [HR=2.09 (95%CI:1.80-2.43)]. Compared with stage Ⅰ NSCLC patients who underwent other surgeries, STAS-positive patients who underwent sublobar resection had a higher risk of 5-year recurrence than patients with other procedures (HR=3.44, 95%CI: 2.49-4.76) and a higher risk of 5-year death (HR=3.40, 95%CI:2.05-5.64); and patients with stage Ⅰ NSCLC who had the pathologic histologic type of squamous carcinoma had a higher risk of 5-year recurrence (HR=2.48,95%CI:1.71-3.60) and a higher risk of 5-year death (HR=3.04, 95%CI: 1.90-4.86) than other patients with the type of squamous lung cancer.

STAS positivity is a risk factor of poor prognosis in patients with stage Ⅰ NSCLC, especially for patients underwent sublobar resection or with squamous lung cancer.

Kallmann syndrome is a type of congenital hypogonadal hypogonadism. Women mostly show primary amenorrhea, pubertal hypodevelopment, hypoolfaction, infertility, etc. This article reports a young female patient with Kallmann syndrome. The patient was admitted to the Department of Endocrinology of Peking Union Medical College Hospital in 2009 due to "primary amenorrhea". The levels of gonadotropin and estrogen were decreased, and luteinizing hormone was not significantly increased after triptorelin stimulation test. Ultrasound showed small uterus, olfactory nerve MRI showed undeveloped olfactory bulb and olfactory tract, pituitary MRI showed no tumor or inflammation, and other anterior pituitary hormones showed no abnormalities. The diagnosis of Kallmann syndrome was clear, and regular estrogen and progesterone replacement therapy was given. In 2022, I successfully conceived and gave birth with gonadotropin-releasing hormone (GnRH) pulse therapy due to fertility requirements. By analyzing and summarizing the diagnosis and treatment of this case, it is suggested that the possibility of Kallmann syndrome should be considered in clinical work for patients with primary amenorrhea with hypoolfactory sense. Correct diagnosis and early treatment will help patients to have successful fertility.

The 42-year-old female was admitted to the Second Hospital of Tianjin Medical University in August 2020 due to "diagnosis of primary myelofibrosis (PMF) for 10 years and aggravation of anemia for half a year". Successively, suspended red blood cells were infused to correct anemia, danazol and erythropoietin were given to promote hematopoiesis, and oral ruxolitinib phosphate was given to target therapy. Half a year later, the anemia progressively aggravated and brown urine appeared. Paroxysmal nocturnal hemoglobinuria (PNH) clones and FLaer results were positive, and PIGA mutation was negative. PMF and PNH clones were diagnosed. One month after the addition of glucocortisol hormone, the patient was withdrawn from blood transfusion. Progression to acute myeloid leukemia M5 (AML-M5) at 24 months of treatment except JAK2^V617FIn addition to mutations in ASXL1 and SRSF2 genes, newly obtained mutations in RUNX1, PTPN11, KRAS and NRAS genes. During the patient's disease progression, JAK2^V617FGene mutation burden and PNH clone expression in granulocyte increased gradually. After treatment with azacitidine combined with veneclax, the patient achieved partial remission. In order to improve the deep remission rate of the patient, allogeneic hematopoietic stem cell transplantation is proposed. This case suggests that the high-risk mutant genes ASXL1, RUNX1, PTPN11, KRAS, and NRAS may cause PMF cells and PNH clones to obtain a "secondary gene mutation strike", promote the proliferation advantage of malignant clones, and may promote the progression of PMF to AML disease.

A 57-year-old male was admitted to Liaoyou Baoshihua Hospital in Panjin, Liaoning Province on August 16, 2022 due to "fatigue with progressive splenomegaly for 1 1/2 years". The results of bone marrow biopsy and second-generation gene sequencing showed deletion of del (5q) in the long arm of chromosome 5, JAK2^V617FMyelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), del (5q) with JAK2 were diagnosed with positive gene mutation and SF3B1 gene mutation, CALR, MPL and SETBP1 mutation^V617FSF3B1 mutation positive. Lenalidomide treatment was recommended to the patient and the patient refused. The patient's blood routine was monitored, and his condition was stable until now.

The patient, male, 76 years old, was admitted to the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) on September 22, 2022 due to "repeated coughing and expectoration for more than 3 months". After treatment, the patient underwent CT-guided percutaneous lung biopsy. After operation, sudden limb weakness and unclear pronunciation occurred. Chest CT examination showed air embolism in the heart and aorta. Immediately, he was given right lateral lying position, head and feet high position, oxygen inhalation, and transferred to intensive care unit for high-flow oxygen therapy, anti-infection, and maintenance of internal environment stability. The patient was discharged after chemotherapy and symptomatic supportive therapy after pulmonary puncture pathological results showed that it was well differentiated mucinous adenocarcinoma. Follow-up for half a year, the patient was treated with chemotherapy on schedule, and the general condition was OK.

Classical myeloproliferative neoplasms (MPN) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), and are a group of malignant clones originating from hematopoietic stem cells. JAK2^V617FThe activation of JAK-STAT signaling pathway caused by mutations such as CALR exon 9 and CALR exon 9 plays an important role in the occurrence and development of MPN disease. Myelofibrosis and leukemia transformation are the main disease progressions of MPN, which seriously affect the survival time and quality of life of patients. In addition to the abnormal inflammatory microenvironment of MPN disease, the imbalance of immune homeostasis in MPN patients has been a hot topic of attention and research in recent years. In this paper, the role and mechanism of innate immune cells and adaptive immune cells in the development of MPN disease were reviewed. There were obvious abnormalities in the number and function of various immune cells in MPN patients, and the immune system was seriously dysregulated, which suggested that the occurrence and progression of MPN were mediated by the weakening of the recognition of abnormal cells, the reduction of specific killing and the immune escape of tumor cells.

Abnormal pro-inflammatory cytokine signaling is a feature of cancer. Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm (MPN) characterized by somatic symptoms, progressive erythropenia, splenomegaly, and an increased risk of evolving into acute leukemia. Dominant myelofibrosis (MF) can also evolve from prefibrous MPN, including polycythemia vera (PV) and essential thrombocythemia (ET). Dysregulation of inflammatory signaling is one of the important reasons leading to the progression of MPN fibrosis. Previous studies have shown that the JAK/STAT and TNF-α/NF-κ B inflammatory pathways jointly promote fibrosis progression in MPN patients, however, how a single cytokine triggers fibrosis and clonal evolution in malignant MPN cells has not been fully elucidated.

Myeloproliferative tumors (MPN) are a group of hematopoietic stem progenitor cell malignant proliferative tumors characterized by uncontrolled expansion of bone marrow cells, elevated blood count, and a high risk of progression to secondary acute myeloid leukemia (sAML). In the majority of patients, mutations in the key MPN-related driver gene (JAK2/CALR/MPL) were detected. The World Health Organization (WHO) classification identifies 3 classical MPNs: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Each of these MPN subtypes exhibits unique clinical, morphological, and molecular characteristics. Despite presenting as hematopoietic stem progenitor cell malignancies, little is known about the disease-causing stem progenitors in MPN.

The study aimed to explore the risk factors that influence the development of thrombotic events in patients with myelofibrosis (sMF) secondary to polycythemia vera (PV) /essential thrombocythemia (ET). The study assessed the incidence and risk factors for thrombosis in 1 258 sMF patients with a median follow-up of 3.5 years, with driver mutations in 1 203 (95.6%) patients, JAK2 mutations in 100% of PPV-MF, JAK2 mutations in 54% (319) of PET-MF, CALR mutations in 191 (33%) and MPL mutations in 52 (9.7%). Fifty-six percent (466/830) and 16% (155/958) of patients received cell-lowering drugs (CT) or JAKi drugs. Of the 466 patients treated with CT, 315 (67.6%) received hydroxyurea (HU), 67 (14.3%) received HU-based combination therapy, and of the 155 patients treated with JAKi medication, 135 (87%) received ruxolitinib (RUX) and 8 (5%) received Rux-based combination therapy. By the time of follow-up, 604 (48%) patients had died, with an annual mortality rate of 9.4%. Prior to the onset of sMF, thrombotic events occurred in 279 (22.2%) patients, including 158 (25.7%) with PV and 121 (18.8%) with ET (P=0.003), 135 (10.7%) patients experienced thrombotic events at a median follow-up time of 3.5 years, with an annual incidence rate of 2.3%.

Myeloproliferative tumors (MPN) are sporadic in most cases, and some germline gene mutations, such as TET-2, TERT, ATG2B/GSKIP, MECOM, HBS1L-MYB and RBBP6, may cause a small number of familial MPN cases. However, the pathogenic germline mutations in most familial MPN cases are unknown.

Myeloproliferative neoplasms (MPN) are a class of diseases that are at high risk of transforming into myelofibrosis (MF) and acute myeloid leukemia (AML). The mechanisms and targets for intervention in their progression are still unclear. The study found that the high mobility group protein A1 (HMGA1) chromatin regulator acts as a participating factor in JAK2^V617FAn epigenetic switch for the progression of mutant MPN, revealing that HMGA1 may serve as a new therapeutic target for MPN.