Review
Oncology
Antonella Bruzzese, Ernesto Vigna, Enrica Antonia Martino, Francesco Mendicino, Eugenio Lucia, Virginia Olivito, Carlo Bova, Angelo Barbato, Gianfranco Filippelli, Isabella Capodanno, Antonino Neri, Fortunato Morabito, Massimo Gentile
Summary: Myelodysplastic syndromes (MDS) are bone marrow malignant disorders characterized by ineffective hematopoiesis and the immune system plays an important role. Recent studies have shown a strong association between MDS with ring sideroblasts (MDS-RS) and SF3B1 mutation. Luspatercept (ACE-536) has shown promising efficacy in treating anemia in MDS patients.
HEMATOLOGICAL ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Tatsuya Konishi, Daichi Sadato, Takashi Toya, Chizuko Hirama, Yuya Kishida, Akihito Nagata, Yuta Yamada, Naoki Shingai, Hiroaki Shimizu, Yuho Najima, Takeshi Kobayashi, Kyoko Haraguchi, Yoshiki Okuyama, Hironori Harada, Kazuteru Ohashi, Yuka Harada, Noriko Doki
Summary: This study analyzed gene mutations and copy number alterations in younger MDS patients and found that these genetic abnormalities can predict clinical outcomes. Higher-risk patients had lower survival rates and higher relapse rates.
SCIENTIFIC REPORTS
(2023)
Article
Biology
Gaurav S. Choudhary, Andrea Pellagatti, Bogos Agianian, Molly A. Smith, Tushar D. Bhagat, Shanisha Gordon-Mitchell, Srabani Sahu, Sanjay Pandey, Nishi Shah, Srinivas Aluri, Ritesh Aggarwal, Sarah Aminov, Leya Schwartz, Violetta Steeples, Robert N. Booher, Murali Ramachandra, Maria Samson, Milagros Carbajal, Kith Pradhan, Teresa Bowman, Manoj M. Pillai, Britta Will, Amittha Wickrema, Aditi Shastri, Robert K. Bradley, Robert E. Martell, Ulrich G. Steidl, Evripidis Gavathiotis, Jacqueline Boultwood, Daniel T. Starczynowski, Amit Verma
Summary: The SF3B1 mutation leads to the expression of a therapeutically targetable, longer, oncogenic IRAK4 isoform in AML/MDS models. This mutation also results in the activation of TRAF6 and NF-kB, promoting the development of leukemia.
Article
Hematology
Courtnee A. Clough, Joseph Pangallo, Martina Sarchi, Janine O. Ilagan, Khrystyna North, Rochelle Bergantinos, Massiel C. Stolla, Jasmine Naru, Patrick Nugent, Eunhee Kim, Derek L. Stirewalt, Arvind R. Subramaniam, Omar Abdel-Wahab, Janis L. Abkowitz, Robert K. Bradley, Sergei Doulatov
Summary: SF3B1 splicing factor mutations are a major cause of ring sideroblasts (RS) formation in myelodysplastic syndromes (MDS). In this study, an induced pluripotent stem cell model of SF3B1-mutant MDS was established, successfully recapitulating RS formation. Mutant SF3B1 induces missplicing of mitochondrial transporters TMEM14C and ABCB7, sequestering iron in mitochondria and causing RS formation.
Review
Oncology
Yan Jiang, Su-Jun Gao, Benoit Soubise, Nathalie Douet-Guilbert, Zi-Ling Liu, Marie-Berengere Troadec
Summary: Gene variants, particularly TP53 mutations, play a crucial role in the prognosis of myelodysplastic syndromes (MDS), being associated with higher risk categories, resistance to traditional therapies, rapid leukemic transformation, and poor outcomes. Current prognosis classification systems for MDS do not consider gene variants, but the impact is significant on the clinical heterogeneity and prognosis of the disease.
Article
Biotechnology & Applied Microbiology
Nida Anwar, Faheem Ahmed Memon, Saba Shahid, Muhammad Shakeel, Muhammad Irfan, Aisha Arshad, Arshi Naz, Ikram Din Ujjan, Tahir Shamsi
Summary: Sequencing studies on MDS patients in Pakistan revealed various genetic mutations associated with myeloid malignancies, including mutations not previously observed in MDS or AML. These findings highlight the importance of molecular profiling in diagnosis and treatment of MDS patients in countries with limited resources like Pakistan. Further research with larger sample sizes is necessary to compare molecular characteristics between Asian and global populations.
Article
Hematology
Mrinal M. Patnaik, Ayalew Tefferi
Summary: Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation, associated with myeloid neoplasms MDS-RS and MDS/MPN-RS-T; SF3B1 mutations are common in these diseases; treatment options include luspatercept for anemia and consideration of aspirin therapy in MDS/MPN-RS-T.
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Review
Oncology
Andrew M. Brunner, Heather A. Leitch, Arjan A. van de Loosdrecht, Nicolas Bonadies
Summary: This review focuses on the diagnosis, prognosis, and treatment options for patients with lower-risk myelodysplastic syndromes (LR-MDS). It discusses the prediction of disease progression and monitoring of treatment response. The review also explores how next-generation sequencing and novel therapies may impact the treatment landscape for LR-MDS, as well as the importance of incorporating structured assessments into routine clinical practice.
BLOOD CANCER JOURNAL
(2022)
Article
Medicine, General & Internal
Jessica Petiti, Federico Itri, Elisabetta Signorino, Antonio Frolli, Carmen Fava, Marco Armenio, Silvia Marini, Emilia Giugliano, Marco Lo Iacono, Giuseppe Saglio, Daniela Cilloni
Summary: Mutations in the SF3B1 gene play a crucial role in the diagnosis and therapy decisions for myelodysplastic syndromes and myeloproliferative neoplasms. However, current sequencing methods are time-consuming and expensive for most small-/medium-sized laboratories. We developed a novel and cost-effective PNA-PCR clamping method that can efficiently identify SF3B1 mutations in these laboratories, guiding patients towards appropriate therapy.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Oncology
Rena Buckstein, Lisa Chodirker, Lee Mozessohn, Karen W. L. Yee, Michelle Geddes, Nancy Zhu, April Shamy, Heather A. Leitch, Grace Christou, Versha Banerji, Leber Brian, Dina Khalaf, Eve St-Hilaire, Nicholas Finn, Thomas Nevill, Mary-Margaret Keating, John Storring, Robert Delage, Anne Parmentier, Aksharh Thambipillai, Mohammed Siddiqui, Christopher Westcott, Chris Cameron, Alexandre Mamedov, Paul Spin, Derek Tang
Summary: This study aimed to assess the natural history of LR myelodysplastic syndromes with ring sideroblasts and revealed a high incidence and mortality rate of this condition in Canada through real-world data.
LEUKEMIA & LYMPHOMA
(2022)
Article
Oncology
Rashmi Kanagal-Shamanna, Guillermo Montalban-Bravo, Koji Sasaki, Faezeh Darbaniyan, Elias Jabbour, Carlos Bueso-Ramos, Yue Wei, Kelly Chien, Tapan Kadia, Farhad Ravandi, Gautam Borthakur, Kelly A. Soltysiak, Mark Routbort, Keyur Patel, Sherry Pierce, L. Jeffrey Medeiros, Hagop Kantarjian, Guillermo Garcia-Manero
Summary: The subtype of SF3B1 mutation plays a key role in risk assessment and prognosis of MDS, with K700E mutation associated with a favorable outcome compared to non-K700E mutations. This highlights the importance of refining MDS subclassification based on different SF3B1 mutation subtypes.
Article
Multidisciplinary Sciences
Nanfang Huang, Yang Song, Wenhui Shi, Juan Guo, Lingyun Wu, Zheng Zhang, Qi He, Xiao Li, Feng Xu
Summary: DHX9 overexpression in myelodysplastic syndromes (MDS) is associated with poor prognosis and high risk of acute myeloid leukemia (AML) transformation. DHX9 is essential for malignant proliferation of leukemia cells. Suppression of DHX9 increases cell apoptosis and sensitizes cells to chemotherapy. Additionally, DHX9 knockdown inactivates PI3K-AKT and ATR-Chk1 signaling, promotes R-loop accumulation, and leads to R-loop-mediated DNA damage.
Review
Medicine, General & Internal
Sandrine Girard, Franck Genevieve, Emmanuelle Rault, Odile Fenneteau, Jean-Francois Lesesve
Summary: Ring sideroblasts are commonly seen in myelodysplastic neoplasms, but they can also occur in other disorders. It is important to be aware of other diseases associated with ring sideroblasts to prevent misdiagnosis and delay in management of different forms of sideroblastic anemia.
Article
Oncology
Vera Adema, Feiyang Ma, Rashmi Kanagal-Shamanna, Natthakan Thongon, Guillermo Montalban-Bravo, Hui Yang, Scott A. Peslak, Feng Wang, Pamela Acha, Francesc Sole, Pamela Lockyer, Margherita Cassari, Jaroslaw P. Maciejewski, Valeria Visconte, Irene Ganan-Gomez, Yuanbin Song, Carlos Bueso-Ramos, Matteo Pellegrini, Tuyet M. Tan, Rafael Bejar, Jennifer S. Carew, Stephanie Halene, Valeria Santini, Gheath Al-Atrash, Karen Clise-Dwyer, Guillermo Garcia-Manero, Gerd A. Blobel, Simona Colla
Summary: SF3B1 mutations in MDS-RS activate the EIF2AK1 pathway, which leads to abnormal erythroid differentiation. Targeting this pathway may rescue red blood cell production.
BLOOD CANCER DISCOVERY
(2022)
Article
Medicine, General & Internal
Huan Li, Fang Hu, Robert Peter Gale, Mikkael A. Sekeres, Yang Liang
Summary: Myelodysplastic syndromes (MDS) are a group of blood cancers characterized by dysregulated hematopoiesis and risk of transformation to acute myeloid leukemia. Prognostic systems can predict survival in MDS patients. Treatment goals differ for low-risk and high-risk MDS, with the aim to improve quality of life and prolong survival, respectively. Hematopoietic cell transplantation can cure MDS, but it is not widely used.
NATURE REVIEWS DISEASE PRIMERS
(2022)