1.Comparative study of orthopaedic robot-assisted minimally invasive surgery and open surgery for limb osteoid osteoma.
Junwei FENG ; Weimin LIANG ; Yue WANG ; Zhi TANG ; MuFuSha A ; Baoxiu XU ; Niezhenghao HE ; Peng HAO
Chinese Journal of Reparative and Reconstructive Surgery 2024;38(1):40-45
OBJECTIVE:
To compare the accuracy and effectiveness of orthopaedic robot-assisted minimally invasive surgery versus open surgery for limb osteoid osteoma.
METHODS:
A clinical data of 36 patients with limb osteoid osteomas admitted between June 2016 and June 2023 was retrospectively analyzed. Among them, 16 patients underwent orthopaedic robot-assisted minimally invasive surgery (robot-assisted surgery group), and 20 patients underwent tumor resection after lotcated by C-arm X-ray fluoroscopy (open surgery group). There was no significant difference between the two groups in the gender, age, lesion site, tumor nidus diameter, and preoperative pain visual analogue scale (VAS) scores ( P>0.05). The operation time, lesion resection time, intraoperative blood loss, intraoperative fluoroscopy frequency, lesion resection accuracy, and postoperative analgesic use frequency were recorded and compared between the two groups. The VAS scores for pain severity were compared preoperatively and at 3 days and 3 months postoperatively.
RESULTS:
Compared with the open surgery group, the robot-assisted surgery group had a longer operation time, less intraoperative blood loss, less fluoroscopy frequency, less postoperative analgesic use frequency, and higher lesion resection accuracy ( P<0.05). There was no significant difference in lesion resection time ( P>0.05). All patients were followed up after surgery, with a follow-up period of 3-24 months (median, 12 months) in the two groups. No postoperative complication such as wound infection or fracture occurred in either group during follow-up. No tumor recurrence was observed during follow-up. The VAS scores significantly improved in both groups at 3 days and 3 months after surgery when compared with preoperative value ( P<0.05). The VAS score at 3 days after surgery was significantly lower in robot-assisted surgery group than that in open surgery group ( P<0.05). However, there was no significant difference in VAS scores at 3 months between the two groups ( P>0.05).
CONCLUSION
Compared with open surgery, robot-assisted resection of limb osteoid osteomas has longer operation time, but the accuracy of lesion resection improve, intraoperative blood loss reduce, and early postoperative pain is lighter. It has the advantages of precision and minimally invasive surgery.
Humans
;
Robotics
;
Osteoma, Osteoid/surgery*
;
Orthopedics
;
Blood Loss, Surgical
;
Retrospective Studies
;
Neoplasm Recurrence, Local
;
Minimally Invasive Surgical Procedures
;
Bone Neoplasms/surgery*
;
Analgesics
;
Treatment Outcome
2.Efficacy and safety of Anlotinib in the treatment of advanced sarcoma.
Qiang YAN ; Wei Tao YAO ; Xin Hui DU ; Liang Yu GUO ; Yi Chao FAN
Chinese Journal of Oncology 2023;45(10):904-910
Objective: Patients with advanced sarcomas have a dismal prognosis with few effective therapies. The purpose of this study was to evaluate the efficacy and safety of anlotinib in the treatment of advanced sarcoma and to explore the relationship between adverse events (AEs) and efficacy. Methods: Data from 45 advanced sarcoma patients who received anlotinib monotherapy at Affiliated Cancer Hospital of Zhengzhou University between June 2018 and August 2021 were retrospectively analyzed. According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, the objective remission rate (ORR) and disease control rate (DCR) were calculated, and the progression free survival (PFS) and treatment-related AEs were recorded and analyzed. Survival analysis was conducted using the Kaplan-Meier survival rates were compared using the Log rank test. Results: Forty patients were treated for more than 1.5 months and received efficacy evaluation. The ORR and DCR after 3 months were 7.5%(3/40) and 80.0%(32/40), respectively. The overall ORR was 2.5%(1/40), the total DCR was 27.5%(11/40), and the median progression-free survival (m-PFS) was 6.70 months; The m-PFS of alveolar soft tissue sarcoma (ASPS) was 10.27 months, which was significantly longer than that of other subtypes of sarcoma (P=0.048). In addition, the DCR of ASPS and synovial sarcoma (SS) was significantly better than that of osteosarcoma (P<0.05). The most common AEs were elevated thyroid stimulating hormone (17.8%, 8/45), anemia (15.6%, 7/45), fatigue (11.1%, 5/45). Five patients developed grade 3 AEs after treatment; The PFS of patients with hand-foot syndrome after treatment was significantly longer than that of patients without hand-foot syndrome (14.10 vs 6.00, P=0.024). Conclusions: The efficacy of anlotinib in the treatment of ASPS and SS is better than that of other subtypes. The PFS in the group with hand-foot syndrome was significantly longer than that of the group without hand-foot syndrome.
Humans
;
Hand-Foot Syndrome
;
Retrospective Studies
;
Sarcoma/drug therapy*
;
Sarcoma, Synovial/drug therapy*
;
Soft Tissue Neoplasms
;
Bone Neoplasms
3.Research progress in the mechanism and treatment of osteosarcoma.
Jichao BIAN ; Yang LIU ; Xiaowei ZHAO ; Chunyang MENG ; Yuanmin ZHANG ; Yangmiao DUAN ; Guodong WANG
Chinese Medical Journal 2023;136(20):2412-2420
Osteosarcoma (OS) is the most common primary malignant bone tumor that more commonly occurs in children and adolescents. The most commonly used treatment for OS is surgery combined with chemotherapy, but the treatment outcomes are typically unsatisfactory. High rates of metastasis and post-treatment recurrence rates are major challenges in the treatment of OS. This underlines the need for studying the in-depth characterization of the pathogenetic mechanisms of OS and development of more effective therapeutic modalities. Previous studies have demonstrated the important role of the bone microenvironment and the regulation of signaling pathways in the occurrence and development of OS. In this review, we discussed the available evidence pertaining to the mechanisms of OS development and identified therapeutic targets for OS. We also summarized the available treatment modalities for OS and identified future priorities for therapeutics research.
Child
;
Adolescent
;
Humans
;
Bone Neoplasms/drug therapy*
;
Signal Transduction
;
Bone and Bones/metabolism*
;
Treatment Outcome
;
Osteosarcoma/drug therapy*
;
Tumor Microenvironment
4.Primary malignant bone tumors incidence, mortality, and trends in China from 2000 to 2015.
Yunfeng XI ; Liying QIAO ; Buqi NA ; Huimin LIU ; Siwei ZHANG ; Rongshou ZHENG ; Wenrui WANG ; Kexin SUN ; Wenqiang WEI ; Jie HE
Chinese Medical Journal 2023;136(17):2037-2043
BACKGROUND:
Primary malignant bone tumors are uncommon, and their epidemiological features are rarely reported. We aimed to study the incidence and death characteristics of bone tumors from 2000 to 2015.
METHODS:
Population-based cancer registries submitted registry data to National Central Cancer Registry of China (NCCRC). The data collected from 501 local cancer registries in China were assessed using NCCRC screening methods and criteria. Incidence and mortality rates of primary bone tumor were stratified by age group, gender, and area. Age-standardized incidence and mortality rates were adjusted using the Chinese standard population in 2000 and Segi's world population. The annual percentage change (APC) in rate was calculated using the Joinpoint Regression Program.
RESULTS:
Data from 368 registries met quality control criteria, of which 134 and 234 were from urban and rural areas, respectively. The data covered 309,553,499 persons. The crude incidence, age-standardized incidence, and crude mortality rates were 1.77, 1.35, and 1.31 per 100,000, respectively. Incidence and mortality rates were higher in males than those in females; they showed downward trends, with declines of 2.2% and 4.8% per year, respectively, and the rates in urban areas were lower than those in rural areas. Significant declining trends were observed in urban areas. Stable trends were seen in rural areas during 2000 to 2007, followed by downward trends. Age-specific incidence and mortality rates showed stable trends in the age group of 0 to 19 years, and downward trends in the age group elder than 19 years.
CONCLUSIONS
The incidence and mortality rates of primary malignant bone tumors in rural areas were higher compared to those in urban areas. Targeted prevention measures are required to monitor and control bone tumor incidence and improve the quality of life of affected patients. This research can provide a scientific basis for the prevention and control of bone tumors, as well as basic information for follow-up research.
Adolescent
;
Adult
;
Child
;
Child, Preschool
;
Female
;
Humans
;
Infant
;
Infant, Newborn
;
Male
;
Young Adult
;
China/epidemiology*
;
Incidence
;
Quality of Life
;
Bone Neoplasms/mortality*
;
East Asian People
5.Characterization of Cell Subsets Associated With Prognosis of Osteosarcoma Based on Single-Cell Sequencing Data.
Sheng-Tao WANG ; Hao-Ran ZHU ; Shu-Juan XU ; Peng GUI ; Ming-Zhou CHEN ; Zhao-Xu LI
Acta Academiae Medicinae Sinicae 2023;45(5):773-782
Objective To explore the cell subsets and characteristics related to the prognosis of osteosarcoma by analyzing the cellular composition of tumor tissue samples from different osteosarcoma patients.Methods The single-cell sequencing data and bulk sequencing data of different osteosarcoma patients were downloaded.We extracted the information of cell samples for dimensionality reduction,annotation,and cell function analysis,so as to identify the cell subsets and clarify the cell characteristics related to the prognosis of osteosarcoma.The development trajectory of macrophages with prognostic significance was analyzed,and the prognostic model of osteosarcoma was established based on the differentially expressed genes of macrophage differentiation.Results The cellular composition presented heterogeneity in the patients with osteosarcoma.The infiltration of mononuclear phagocytes in osteosarcoma had prognostic significance(P=0.003).Four macrophage subsets were associated with prognosis,and their signature transcription factors included RUNX3(+),ETS1(+),HOXD11(+),ZNF281(+),and PRRX1(+).Prog_Macro2 and Prog_Macro4 were located at the end of the developmental trajectory,and the prognostic ability of macrophage subsets increased with the progression of osteosarcoma.The prognostic model established based on the differentially expressed genes involved in macrophage differentiation can distinguish the survival rate of osteosarcoma patients with different risks(P<0.001).Conclusion Macrophage subsets are closely related to the prognosis of osteosarcoma and can be used as the key target cells for the immunotherapy of osteosarcoma.
Humans
;
Prognosis
;
Osteosarcoma/genetics*
;
Immunotherapy
;
Macrophages
;
Transcription Factors
;
Bone Neoplasms/genetics*
;
Homeodomain Proteins
;
Repressor Proteins
6.Three-dimensional-printed hemi-pelvic prosthesis for revision of aseptic loosening or screw fracture of modular hemi-pelvic prosthesis.
Xin LIU ; Yi LUO ; Xuanhong HE ; Jie WANG ; Zhuangzhuang LI ; Yuqi ZHANG ; Xin HU ; Minxun LU ; Fan TANG ; Yong ZHOU ; Li MIN ; Chongqi TU
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(10):1183-1189
OBJECTIVE:
To investigate the effectiveness of three-dimensional (3D)-printed hemi-pelvic prosthesis for revision of aseptic loosening or screw fracture of modular hemi-pelvic prosthesis.
METHODS:
Between February 2017 and January 2020, 11 patients with aseptic loosening or screw fracture of modular hemi-pelvic prosthesis were revised using 3D-printed hemi-pelvic prostheses. There were 7 males and 4 females with an average age of 44 years (range, 25-60 years). In the first operation, all patients underwent total tumor resection, modular hemi-pelvic prosthesis reconstruction, and autologous femoral head transplantation. According to the Enneking pelvic partition system, 8 cases were resected in zones Ⅰ+Ⅱ and 3 cases in zones Ⅰ+Ⅱ+Ⅲ. The interval from the initial operation to this revision ranged from 14.3-66.2 months, with an average of 35.8 months. The operation time, the amount of intraoperative bleeding, and the occurrence of complications were recorded. At 6 months after the first operation, before revision, and at last follow-up, the American Musculoskeletal Tumor Society (MSTS) score and Harris score were used to evaluate the recovery of lower limb function. The pain-free walking distance of patients without brace assistance was recorded at last follow-up. X-ray films were taken at 1 month after the first operation, before revision, and at 1 month after revision, the acetabulum position was assessed by the differences in weight arm and cup height between bilateral hip joints. At last follow-up, the digital X-ray tomography was taken to evaluate the prosthesis-bone integration and the occurrence of aseptic loosening.
RESULTS:
The operation time was 182.6-238.0 minutes (mean, 197.4 minutes). The amount of intraoperative bleeding was 400-860 mL (mean, 550.0 mL). All incisions healed by first intention with no infection, hip dislocation, nerve damage, or vascular-related adverse events. The MSTS score and Harris score at last follow-up were significantly higher than those at 6 months after the first operation and before revision ( P<0.05), while the score before revision was significantly lower than that at 6 months after the first operation ( P<0.05). At last follow-up, the patients were able to walk more than 1 000 meters painlessly without brace assistance. Imaging review showed that the difference of cup height at 1 month after revision was significantly lower than that at 1 month after the first operation and before revision, and at 1 month after the first operation than before revision operation, and the differences were significant ( P<0.05). There was no significant difference in the difference of weight arm among three time points ( P>0.05). All prostheses were well integrated, and no aseptic loosening of the prosthesis or screw fracture occurred.
CONCLUSION
Revision with 3D-printed hemi-pelvic prostheses benefited in reconstructing stable pelvic ring and natural bodyweight transmission for patients encountering the aseptic loosening or screw fracture of modular hemi-pelvic prosthesis. Early postoperative rehabilitation training can maximize the recovery of patient limb function, reduce pain during walking, and reduce the incidence of complications.
Male
;
Female
;
Humans
;
Adult
;
Arthroplasty, Replacement, Hip/methods*
;
Hip Prosthesis
;
Treatment Outcome
;
Prosthesis Failure
;
Fractures, Bone/surgery*
;
Retrospective Studies
;
Neoplasms
7.Long-term effectiveness of uncemented allograft-prosthesis composite for reconstruction of bone defects after proximal femur tumor resection.
Yang WANG ; Minxun LU ; Yuqi ZHANG ; Xuanhong HE ; Zhuangzhuang LI ; Taojun GONG ; Yitian WANG ; Yong ZHOU ; Yi LUO ; Fan TANG ; Wenli ZHANG ; Hong DUAN ; Chongqi TU ; Li MIN
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(10):1190-1197
OBJECTIVE:
To investigate the long-term effectiveness of uncemented allograft-prosthesis composite (APC) for reconstruction of bone defects after proximal femur tumor resection.
METHODS:
Between June 2007 and March 2014, 21 patients who underwent uncemented APC reconstruction of proximal femur after tumor resection were retrospectively evaluated. There were 9 males and 12 females with an average age of 33.2 years (range, 19-54 years). There were 9 cases of giant cell tumor of bone, 5 cases of osteosarcoma, 4 cases of osteoblastic osteosarcoma, 2 cases of chondrosarcoma, and 1 case of undifferentiated pleomorphic sarcoma. Thirteen cases of benign bone tumors were all classified as stage 3 by Enneking staging; and 8 cases of malignant bone tumors were classified as grade ⅡB in 7 cases and grade ⅡA in 1 case according to the American Joint Committee on Cancer (AJCC) staging system. Among them, 7 patients underwent reoperation after recurrence, and the rest were primary operations; 8 patients presented with pathological fractures. The preoperative Harris hip score (HHS) and American Musculoskeletal Tumor Society (MSTS) score was 40 (30, 49) and 9.1±3.5, respectively. The length of osteotomy was 80-154 mm, with an average of 110 mm. At 1 year after operation and last follow-up, HHS and MSTS scores were utilized to evaluate the function of hip joint; the gluteus medius strength score was used to evaluation of the hip abduction function. Image examinations were taken at 1, 3, 6, 9, and 12 months after operation and every year thereafter to assess the union of allograft-host bone interfaces. Intra- and post-operative complications were also recorded.
RESULTS:
All patients were followed up 84-163 months (mean, 123.5 months). At 1 year after operation and last follow-up, the HHS and MSTS scores significantly improved when compared with the preoperative scores ( P<0.05). However, there was no significant difference in the HHS score, MSTS score, and gluteus medius strength score between the two time points after operation ( P>0.05). Image examination showed that all allograft-host bone interfaces achieved union after 5-10 months (mean, 7.6 months). At last follow-up, all patients had bone resorption, including 11 severe cases, 4 moderate cases, and 6 mild cases; the bone resorption sites included Gruen 1, 2, and 7 regions. Complications included 10 fractures and 1 prosthetic fracture. Local recurrence occurred in 3 patients and pulmonary metastasis in 3 patients.
CONCLUSION
Uncemented APC is a reliable method for the reconstruction of bone defects after proximal femur tumor resection. It has the good long-term effectiveness and possesses obvious advantages in the union at the bone-bone surface.
Adult
;
Female
;
Humans
;
Male
;
Allografts/pathology*
;
Bone Neoplasms/surgery*
;
Bone Resorption/pathology*
;
Bone Transplantation/methods*
;
Femur/surgery*
;
Osteosarcoma/pathology*
;
Prostheses and Implants
;
Retrospective Studies
;
Treatment Outcome
;
Young Adult
;
Middle Aged
8.Short-term effectiveness of orthopedic robot-assisted resection for osteoid osteoma.
Zhuoyu LI ; Weifeng LIU ; Zhiping DENG ; Tao JIN ; Yang SUN ; Yongkun YANG ; Yuan LI ; Fajun YANG ; Feng YU ; Lin HAO ; Qing ZHANG ; Xiaohui NIU
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(11):1319-1325
OBJECTIVE:
To investigate short-term effectiveness and clinical application advantages of orthopedic robot-assisted resection for osteoid osteoma compared with traditional open surgery.
METHODS:
A retrospective analysis was conducted on clinical data of 48 osteoid osteoma patients who met the selection criteria between July 2022 and April 2023. Among them, 23 patients underwent orthopedic robot-assisted resection (robot-assisted surgery group), and 25 patients received traditional open surgery (traditional surgery group). There was no significant difference ( P>0.05) in gender, age, disease duration, lesion location and size, and preoperative visual analogue scale (VAS) score, and musculoskeletal tumor society (MSTS) score between the two groups. The surgical time, intraoperative blood loss, intraoperative lesion localization time, initial localization success rate, infection, and recurrence were recorded and compared. VAS scores before surgery and at 24 hours, 1, 3, 6, and 9 months after surgery and MSTS score before surgery and at 3 months after surgery were assessed.
RESULTS:
All patients completed the surgery successfully, with no significant difference in surgical time between the two groups ( P>0.05). Compared to the traditional surgery group, the robot-assisted surgery group had less intraoperative blood loss, shorter lesion localization time, and shorter hospitalization time, with significant differences ( P<0.05). The initial localization success rate was higher in the robot-assisted surgery group than in the traditional surgery group, but the difference between the two groups was not significant ( P>0.05). All patients in both groups were followed up, with the follow-up time of 3-12 months in the robot-assisted surgery group (median, 6 months) and 3-14 months in the traditional surgery group (median, 6 months). The postoperative MSTS scores of both groups improved significantly when compared to those before surgery ( P<0.05), but there was no significant difference in the changes in MSTS scores between the two groups ( P>0.05). The postoperative VAS scores of both groups showed a gradually decreasing trend over time ( P<0.05), but there was no significant difference between the two groups after surgery ( P>0.05). During follow-up, except for 1 case of postoperative infection in the traditional surgery group, there was no infections or recurrences in other cases. There was no significant difference in the incidence of postoperative infection between the two groups ( P>0.05).
CONCLUSION
Orthopedic robot-assisted osteoid osteoma resection achieves similar short-term effectiveness when compared to traditional open surgery, with shorter lesion localization time.
Humans
;
Robotics
;
Blood Loss, Surgical
;
Osteoma, Osteoid/surgery*
;
Retrospective Studies
;
Treatment Outcome
;
Postoperative Complications
;
Bone Neoplasms/surgery*
9.Research progress of new multifunctional bone cement in bone tumor therapy.
Ruilong SUN ; Yunfei LI ; Yongzheng TIAN ; Bo FAN
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(11):1444-1450
OBJECTIVE:
The research progress of new multifunctional bone cement in bone tumor therapy in recent years was reviewed, in order to provide help for the future research of anti-tumor bone cement.
METHODS:
The related literature on the treatment of bone tumors with new multifunctional bone cement at home and abroad in recent years was extensively reviewed and summarized.
RESULTS:
The new multifunctional bone cements include those with the functions of photothermotherapy, magnetic thermotherapy, chemoradiotherapy, and antibacterial after operation, which are discussed from the aspects of anti-tumor, drug controlled release, and cytotoxicity. Controlled drug release has been achieved in multifunctional bone cements by adjusting heat and pH or incorporating particles such as chitosan oligosaccharides and γ-cyclodextrin. At present, multifunctional bone cement with hyperthermia, radiotherapy, and chemotherapy has effectively inhibited the local recurrence and distant metastasis of bone tumors. Broadening the application of bone cement for photothermal and magnetic thermal therapy to deeper bone tumors, investigating more precise controlled release of drug-loaded bone cement, and introducing nanoparticles with both thermal conversion and intrinsic enzymatic activities into bone cement for synergistic anti-tumor therapy are promising research directions.
CONCLUSION
The new multifunctional bone cement inhibits bone tumor cells, promotes new bone formation in bone defects, and prevents incision infection after tumor resection. Certain progress has been made in anti-tumor, antibacterial, drug-controlled release, and reduction of cytotoxicity. Expanding the deeper application range of the new multifunctional bone cement, verifying the safety in clinical application, and focusing on the individualized treatment of the new multifunctional bone cement are the problems that need to be solved in the future.
Humans
;
Bone Cements/therapeutic use*
;
Delayed-Action Preparations
;
Bone Neoplasms/therapy*
;
Anti-Bacterial Agents/therapeutic use*
;
Nanoparticles/therapeutic use*
10.Construction of a Mouse Model for Myeloproliferative Neoplasms and an Evaluation System.
Shu-Jin WANG ; Xiang-Ru YU ; Qi-Gang ZHANG ; Yan-Jie LI ; Chun-Ling FU ; Kai-Lin XU
Journal of Experimental Hematology 2023;31(4):1113-1118
OBJECTIVE:
To construct a myeloproliferative neoplasms (MPN) transplanted mouse model with JAK2-V617F, MPLW515L or CALR-Type I gene mutation, and establish a systematic evaluation system to verify the success of model construction.
METHODS:
The bone marrow c-kit+ cells of the mice were obtained by the following steps: The mice were killed by cervical dislocation, the femur, tibia and ilium were separated, and the bone marrow cells were collected. The c-kit+ cells were sorted after incubation with CD117 magnetic beads. The method of constructing mouse primary mutant cells is as follows: A gene mutation vector with a GFP tag was constructed by the retroviral system, and the retroviral vector was packaged into the Platinum-E cells to obtain the virus supernatant, and then used it to infect the c-kit+ cells of mice. The MPN mouse model was constructed as follows: the mouse primary c-kit+ cells containing the mutant genes were collected after infection, and then transplanted them via the tail vein into the female recipient mice of the same species which were irradiated with a lethal dose of gamma rays (8.0 Gy). The MPN mouse model was evaluated as follows: After transplantation, the peripheral blood of the mice was regularly collected from the tail vein to perform the complete blood count test, and the size of spleen and the degree of bone marrow fibrosis were estimated.
RESULTS:
The mouse c-kit+ cells with the mutant genes were successfully obtained from the bone marrow. MPN mouse model was successfully constructed: The peripheral blood cells of the MPN-transplanted mice carried exogenous implanted GFP-positive cells, and the white blood cells (WBC), platelet (PLT) and hematocrit (HCT) were all increased; the body weight loss, and the water and food intake were reduced in the transplanted mice; further pathological analysis showed that the transplanted mice displayed splenomegaly and bone marrow fibrosis. These results suggested that the MPN mouse model was successfully constructed. According to the common and different characteristics of the three MPN mouse model, a preliminary evaluation system for judging the success of MPN mouse model construction was summarized, which mainly included the following indicators, for example, the proportion of GFP-positive cells in the peripheral blood of mice; WBC, PLT and HCT; the degree of spleen enlargement and the bone marrow fibrosis.
CONCLUSION
The MPN mouse model with JAK2-V617F, MPLW515L or CALR-Type I gene mutation is successfully established by retroviral system, which can provide an important experimental animal model for the research of MPN pathogenesis and drug-targeted therapy.
Female
;
Mice
;
Animals
;
Primary Myelofibrosis
;
Myeloproliferative Disorders/genetics*
;
Bone Marrow/pathology*
;
Mutation
;
Disease Models, Animal
;
Neoplasms
;
Janus Kinase 2/genetics*

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