The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma.
The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma.
复制标题
复发难治性多发性骨髓瘤的遗传异质性和耐药机制。
DOI：
10.1038/s41467-022-31430-0
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发表时间：
2022-06-29
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
Multiple myeloma is the second most common hematological malignancy. Despite significant advances in treatment, relapse is common and carries a poor prognosis. Thus, it is critical to elucidate the genetic factors contributing to disease progression and drug resistance. Here, we carry out integrative clinical sequencing of 511 relapsed, refractory multiple myeloma (RRMM) patients to define the disease’s molecular alterations landscape. The NF-κB and RAS/MAPK pathways are more commonly altered than previously reported, with a prevalence of 45–65% each. In the RAS/MAPK pathway, there is a long tail of variants associated with the RASopathies. By comparing our RRMM cases with untreated patients, we identify a diverse set of alterations conferring resistance to three main classes of targeted therapy in 22% of our cohort. Activating mutations in IL6ST are also enriched in RRMM. Taken together, our study serves as a resource for future investigations of RRMM biology and potentially informs clinical management. The genetic factors involved in disease progression and drug resistance in multiple myeloma (MM) are varied and complex. Here, genomic and transcriptomic profiling of 511 relapsed and refractory MM patients reveals genetic alterations in several oncogenic pathways contributing to progression and resistance to MM therapies.
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影响因子：
7
作者：
Cieslik M;Chugh R;Wu YM;Wu M;Brennan C;Lonigro R;Su F;Wang R;Siddiqui J;Mehra R;Cao X;Lucas D;Chinnaiyan AM;Robinson D
通讯作者：
Robinson D
影响因子：
28.4
作者：
Cobain EF;Wu YM;Vats P;Chugh R;Worden F;Smith DC;Schuetze SM;Zalupski MM;Sahai V;Alva A;Schott AF;Caram MEV;Hayes DF;Stoffel EM;Jacobs MF;Kumar-Sinha C;Cao X;Wang R;Lucas D;Ning Y;Rabban E;Bell J;Camelo-Piragua S;Udager AM;Cieslik M;Lonigro RJ;Kunju LP;Robinson DR;Talpaz M;Chinnaiyan AM
通讯作者：
Chinnaiyan AM
影响因子：
5.4
作者：
Dentro, Stefan C.;Wedge, David C.;Van Loo, Peter
通讯作者：
Van Loo, Peter
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
39.2
作者：
ALEXANIAN, R;BARLOGIE, B;DIXON, D
通讯作者：
DIXON, D