Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
X
X
publication

Biological and clinical significance of dysplastic hematopoiesis in patients with newly-diagnosed multiple myeloma


Maia, C. et al.
CIMA, Spain
Blood (2020)

Risk of developing myelodysplastic syndromes (MDS) is significantly increased in both multiple myeloma (MM) and MGUS, suggesting that is therapy independent. However, the incidence and sequelae of dysplastic hematopoiesis at diagnosis are unknown. Here, we used multidimensional flow cytometry (MFC) to prospectively screen for presence of MDS-associated phenotypic alterations (MDS-PA) in the bone marrow of 285 MM patients enrolled in the PETHEMA/GEM2012MENOS65 trial (NCT01916252), and investigated the clinical significance of monocytic MDS-PA in a larger series of 1,252 patients enrolled in four PETHEMA/GEM protocols. At diagnosis, 33/285 (11.6%) cases displayed MDS-PA. Bulk- and single-cell targeted sequencing of MDS recurrently mutated genes in CD34+ progenitors (and dysplastic lineages) from 67 patients unveiled clonal hematopoiesis in 13/26 (50%) cases with MDS-PA versus 9/41 (22%) without MDS-PA; TET2 and NRAS were the most frequently mutated genes. Dynamics of MDS-PA at diagnosis and after autologous transplant were evaluated in 86/285 patients, and showed that in most cases (69/86, 80%) MDS-PA either persisted or remained absent in patients with or without MDS-PA at diagnosis, respectively. Noteworthy, MDS-associated mutations unfrequently emerged after high-dose therapy. Based on MFC profiling, we found that patients with MDS-PA have altered hematopoiesis and Treg distribution in the tumor microenvironment. Importantly, presence of monocytic MDS-PA at diagnosis anticipated greater risk of hematological toxicity and was independently associated with inferior progression-free (HR:1.5, P=.02) and overall survival (HR:1.7, P=.01). This study unveils the biological and clinical significance of dysplastic hematopoiesis in newly-diagnosed MM, which can be screened with moderate sensitivity using cost-effective MFC.


DOWNLOAD
publication
Distinct genetic pathways define pre-leukemic and compensatory clonal hematopoiesis in Shwachman-Diamond syndrome
Kennedy, A. L. et al.
publication
Molecular mechanisms mediating relapse following ivosidenib monotherapy in IDH1-mutant relapsed or refractory AML
Choe, S. et al.
publication
Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML
DiNardo, C. D. et al.
publication
Single-cell mutational profiling enhances the clinical evaluation of AML MRD
Ediriwickrema, A. et al.
REQUEST QUOTE