TY  - JOUR
A1  - Solimando, Antonio Giovanni
A1  - Da Vià, Matteo Claudio
A1  - Bolli, Niccolò
A1  - Steinbrunn, Torsten
T1  - The route of the malignant plasma cell in its survival niche: exploring “Multiple Myelomas”
JF  - Cancers
N2  - Growing evidence points to multiple myeloma (MM) and its stromal microenvironment using several mechanisms to subvert effective immune and anti-tumor responses. Recent advances have uncovered the tumor-stromal cell influence in regulating the immune-microenvironment and have envisioned targeting these suppressive pathways to improve therapeutic outcomes. Nevertheless, some subgroups of patients include those with particularly unfavorable prognoses. Biological stratification can be used to categorize patient-, disease- or therapy-related factors, or alternatively, these biological determinants can be included in a dynamic model that customizes a given treatment to a specific patient. Genetic heterogeneity and current knowledge enforce a systematic and comprehensive bench-to-bedside approach. Given the increasing role of cancer stem cells (CSCs) in better characterizing the pathogenesis of solid and hematological malignancies, disease relapse, and drug resistance, identifying and describing CSCs is of paramount importance in the management of MM. Even though the function of CSCs is well-known in other cancer types, their role in MM remains elusive. With this review, we aim to provide an update on MM homing and resilience in the bone marrow micro milieu. These data are particularly interesting for clinicians facing unmet medical needs while designing novel treatment approaches for MM.
KW  - multiple myeloma
KW  - cell of origin
KW  - cancer stem cells
KW  - bone marrow homing
KW  - adhesion molecule
KW  - bone marrow immune-microenvironment
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281728
SN  - 2072-6694
VL  - 14
IS  - 13
ER  - 
TY  - JOUR
A1  - Walker, Brian A.
A1  - Mavrommatis, Konstantinos
A1  - Wardell, Christopher P.
A1  - Ashby, T. Cody
A1  - Bauer, Michael
A1  - Davies, Faith
A1  - Rosenthal, Adam
A1  - Wang, Hongwei
A1  - Qu, Pingping
A1  - Hoering, Antje
A1  - Samur, Mehmet
A1  - Towfic, Fadi
A1  - Ortiz, Maria
A1  - Flynt, Erin
A1  - Yu, Zhinuan
A1  - Yang, Zhihong
A1  - Rozelle, Dan
A1  - Obenauer, John
A1  - Trotter, Matthew
A1  - Auclair, Daniel
A1  - Keats, Jonathan
A1  - Bolli, Niccolo
A1  - Fulciniti, Mariateresa
A1  - Szalat, Raphael
A1  - Moreau, Phillipe
A1  - Durie, Brian
A1  - Stewart, A. Keith
A1  - Goldschmidt, Hartmut
A1  - Raab, Marc S.
A1  - Einsele, Hermann
A1  - Sonneveld, Pieter
A1  - San Miguel, Jesus
A1  - Lonial, Sagar
A1  - Jackson, Graham H.
A1  - Anderson, Kenneth C.
A1  - Avet-Loiseau, Herve
A1  - Munshi, Nikhil
A1  - Thakurta, Anjan
A1  - Morgan, Gareth
T1  - A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis
JF  - Leukemia
N2  - Patients with newly diagnosed multiple myeloma (NDMM) with high-risk disease are in need of new treatment strategies to improve the outcomes. Multiple clinical, cytogenetic, or gene expression features have been used to identify high-risk patients, each of which has significant weaknesses. Inclusion of molecular features into risk stratification could resolve the current challenges. In a genome-wide analysis of the largest set of molecular and clinical data established to date from NDMM, as part of the Myeloma Genome Project, we have defined DNA drivers of aggressive clinical behavior. Whole-genome and exome data from 1273 NDMM patients identified genetic factors that contribute significantly to progression free survival (PFS) and overall survival (OS) (cumulative R2 = 18.4% and 25.2%, respectively). Integrating DNA drivers and clinical data into a Cox model using 784 patients with ISS, age, PFS, OS, and genomic data, the model has a cumlative R2 of 34.3% for PFS and 46.5% for OS. A high-risk subgroup was defined by recursive partitioning using either a) bi-allelic TP53 inactivation or b) amplification (≥4 copies) of CKS1B (1q21) on the background of International Staging System III, comprising 6.1% of the population (median PFS = 15.4 months; OS = 20.7 months) that was validated in an independent dataset. Double-Hit patients have a dire prognosis despite modern therapies and should be considered for novel therapeutic approaches.
KW  - cancer genomics
KW  - risk factors
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233299
VL  - 33
ER  -