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Open, Single Arm, Multicenter, Phase 2 Trial to Evaluate Efficacy and Safety of NB02 (Poseltinib) Combined with Rituximab and Lenalidomide As a Salvage Therapy for Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma

An Open, Single treatment arm, Multi-center, Prospective, Phase 2 Trial to Evaluate Efficacy and Safety of NB02 (Poseltinib) combined with Rituximab and Lenalidomide as a Salvage Therapy for Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma

开始日期2024-11-25

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NOBO Medicine Inc.

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3

项与 NOBO Medicine Inc. 相关的文献（医药）

2024-11-01·iScience

Machine-learning-based predictive classifier for bone marrow failure syndrome using complete blood count data

Article

作者: Kim, Myungshin ; Koh, Youngil ; Seo, Jeongmin ; Lee, Chansub ; Lee, Jong-Mi ; An, Hongyul ; Sun, Choong Hyun ; An, Hong Yul

Accurate risk assessment of bone marrow failure syndrome (BMFS) is crucial for early diagnosis and intervention. Interpreting complete blood count (CBC) data is challenging without hematological expertise. To support primary physicians, we developed a predictive model using basic demographics and CBC data collected retrospectively from two major hospitals in South Korea. Binary classifiers for aplastic anemia and myelodysplastic syndrome were created and combined to form a BMFS classifier. The model demonstrated high performance in distinguishing BMFS, with consistent results across different CBC feature sets, confirmed by external validation. This algorithm provides a practical guide for primary physicians to identify BMFS based on initial CBC data, aiding in effective triage, timely referrals, and improved patient care.

International Journal of Molecular Sciences

Influence of the Bone Marrow Microenvironment on Hematopoietic Stem Cell Behavior Post-Allogeneic Transplantation: Development of Clonal Hematopoiesis and Telomere Dynamics

Article

作者: Lee, Jong-Mi ; Hong, Yuna ; Kwag, Daehun ; Sun, Choong Hyun ; Park, Silvia ; Kim, Hoon Seok ; Lee, Chaeyeon ; Kim, Yoo-Jin ; An, Hongyul ; Kang, Dain ; Kim, Myungshin ; Koh, Youngil ; Na, Duyeon ; Kim, Yonggoo

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential cure for myelodysplastic neoplasms (MDSs) and other hematologic malignancies. This study investigates post-transplantation genetic evolution and telomere dynamics in hematopoietic cells, with a focus on clonal hematopoiesis (CH). We conducted a longitudinal analysis of 21 MDS patients who underwent allo-HSCT between September 2009 and February 2015. Genetic profiles of hematopoietic cells from both recipients and donors were compared at equivalent pre- and post-transplantation time points. Targeted sequencing identified CH-associated mutations, and real-time quantitative PCR measured telomere length. Furthermore, we compared CH incidence between recipients and age-matched controls from the GENIE cohort from routine health checkups. Post-allo-HSCT, 38% of recipients developed somatic mutations not detected before transplantation, indicating de novo CH originating from donor cells. Compared to age-matched healthy controls, recipients showed a significantly higher incidence of CH, suggesting increased susceptibility to genetic changes post-transplant. Telomere length analysis also revealed accelerated shortening in transplanted cells, highlighting the heightened stress and proliferation demands in the new microenvironment. Our findings reveal a notable incidence of donor-derived CH in allo-HSCT recipients, alongside significant telomere attrition. This suggests the potential influence of the marrow microenvironment on genetic and molecular changes in hematopoietic cells.

npj Parkinson's Disease

Parkinson’s disease is associated with clonal hematopoiesis with TET2 mutation

Article

作者: Sun, Choonghyun ; Lim, Jiwoo ; Jeon, Beomseok ; Im, Hogune ; Koh, Youngil ; Shin, Jung Hwan ; Choi, Su-Yeon ; Lee, Chan Young ; Kim, Han-Joon ; An, Hongyul ; Woo, Kyung Ah

Clonal hematopoiesis of indeterminate potential (CHIP), a premalignant expansion of mutated hematopoietic stem cells, is linked to immune alterations. Given the role of neuroinflammation and immune dysfunction in Parkinson's disease (PD), we hypothesized a connection between CHIP and PD. We analyzed peripheral blood DNA from 341 PD, 92 isolated REM sleep behavior disorder (iRBD) patients, and 5003 controls using targeted sequencing of 24 genes associated with hematologic neoplasms. PD cases were classified by clinical progression mode: fast, slow, and typical. Using multivariable logistic regression models, CHIP prevalence was assessed against controls with a 1.0% variant allele fraction threshold. CHIP with TET2 mutations was more prevalent in PD than controls (aOR 1.75, 95% CI 1.11-2.77, p = 0.017), particularly in the fast motor progression subgroup (aOR 3.19, p = 0.004). No distinct associations were observed with iRBD. PD is linked to increased odds of CHIP with TET2 mutations, suggesting immune dysregulation in PD pathophysiology.

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