The recognition of host genetic factors underlying susceptibility to hematopoietic malignancies has increased greatly over the last decade. Historically, germline predisposition was thought to primarily affect the young. However, emerging data indicate that hematopoietic malignancies that develop in people of all ages across the human lifespan can derive from germline predisposing conditions and are not exclusively observed in younger individuals. The age at which hematopoietic malignancies manifest appears to correlate with distinct underlying biological pathways. Progression from having a deleterious germline variant to being diagnosed with overt malignancy involves complex, multistep gene-environment interactions with key external triggers, such as infection and inflammatory stimuli, driving clonal progression. Understanding the mechanisms by which predisposed clones transform under specific pressures may reveal strategies to better treat and even prevent hematopoietic malignancies from occurring.Recent unbiased genome-wide sequencing studies of children and adults with hematopoietic malignancies have revealed novel genes in which disease-causing variants are of germline origin. This paradigm shift is spearheaded by findings in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) as well as acute lymphoblastic leukemia, but it also encompasses other cancer types. Although not without challenges, the field of genetic cancer predisposition is advancing quickly, and a better understanding of the genetic basis of hematopoietic malignancies risk affects therapeutic decisions as well as genetic counseling and testing of at-risk family members.
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http://dx.doi.org/10.1158/2159-8290.CD-23-1091 | DOI Listing |
Front Oncol
January 2025
School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan, China.
Multiple Myeloma (MM) is the second most common malignancy of the hematopoietic system, accounting for approximately 10% of all hematological malignancies, and currently, there is no complete cure. Existing research indicates that exosomal long non-coding RNAs (lncRNAs) play a crucial regulatory role in the initiation and progression of tumors, involving various interactions such as lncRNA-miRNA, lncRNA-mRNA, and lncRNA-RNA binding proteins (RBP). Despite the significant clinical application potential of exosomal lncRNAs, research in this area still faces challenges due to their low abundance and technical limitations.
View Article and Find Full Text PDFBlood Cancer J
January 2025
Université de Toulouse 3 Paul Sabatier, Cancer Research Centre of Toulouse, UMR1037 Inserm, UMR5077 CNRS, Equipe Labellisée Ligue Nationale Contre le Cancer 2023, Equipe labélisée Institut Carnot Opale, 31037, Toulouse, France.
GATA2 germline mutations lead to a syndrome characterized by immunodeficiency, vascular disorders and myeloid malignancies. To elucidate how these mutations affect hematopoietic homeostasis, we created a knock-in mouse model expressing the recurrent Gata2 R396Q missense mutation. Employing molecular and functional approaches, we investigated the mutation's impact on hematopoiesis, revealing significant alterations in the hematopoietic stem and progenitor (HSPC) compartment in young age.
View Article and Find Full Text PDFIntroduction: The real-world safety profiles of the demethylating agents Azacitidine and Decitabine remain inadequately characterized despite their widespread clinical use. Both drugs are extensively employed for the treatment of hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). This study aims to evaluate their adverse event (AE) profiles by leveraging data from the U.
View Article and Find Full Text PDFMAbs
December 2025
Ichnos Glenmark Innovation, New York, NY, USA.
ISB 1442 is a bispecific biparatopic antibody in clinical development to treat hematological malignancies. It consists of two adjacent anti-CD38 arms targeting non-overlapping epitopes that preferentially drive binding to tumor cells and a low-affinity anti-CD47 arm to enable avidity-induced blocking of proximal CD47 receptors. We previously reported the pharmacology of ISB 1442, designed to reestablish synthetic immunity in CD38+ hematological malignancies.
View Article and Find Full Text PDFJ Bras Nefrol
January 2025
Universidade Federal de São Paulo (UNIFESP), Departamento de Medicina, Divisão de Nefrologia, São Paulo, SP, Brazil.
Introduction: Glomerular diseases can be associated with solid or hematopoietic malignancies. The prevalence of these associations varies according to the studied glomerular disease. This study aimed to evaluate the frequency and type of neoplasms in patients with glomerular diseases as well as their clinical, laboratory, and histopathological features and the relationship with immunosuppressive therapy.
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