• Je něco špatně v tomto záznamu ?

Identification of disease-related aberrantly spliced transcripts in myeloma and strategies to target these alterations by RNA-based therapeutics

D. Ogiya, Z. Chyra, SJ. Verselis, M. O'Keefe, J. Cobb, I. Abiatari, S. Talluri, AA. Sithara, T. Hideshima, MP. Chu, R. Hájek, DM. Dorfman, LM. Pilarski, KC. Anderson, S. Adamia

. 2023 ; 13 (1) : 23. [pub] 20230203

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc23004254

Novel drug discoveries have shifted the treatment paradigms of most hematological malignancies, including multiple myeloma (MM). However, this plasma cell malignancy remains incurable, and novel therapies are therefore urgently needed. Whole-genome transcriptome analyses in a large cohort of MM patients demonstrated that alterations in pre-mRNA splicing (AS) are frequent in MM. This manuscript describes approaches to identify disease-specific alterations in MM and proposes RNA-based therapeutic strategies to eradicate such alterations. As a "proof of concept", we examined the causes of aberrant HMMR (Hyaluronan-mediated motility receptor) splicing in MM. We identified clusters of single nucleotide variations (SNVs) in the HMMR transcript where the altered splicing took place. Using bioinformatics tools, we predicted SNVs and splicing factors that potentially contribute to aberrant HMMR splicing. Based on bioinformatic analyses and validation studies, we provided the rationale for RNA-based therapeutic strategies to selectively inhibit altered HMMR splicing in MM. Since splicing is a hallmark of many cancers, strategies described herein for target identification and the design of RNA-based therapeutics that inhibit gene splicing can be applied not only to other genes in MM but also more broadly to other hematological malignancies and solid tumors as well.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc23004254
003      
CZ-PrNML
005      
20230425141236.0
007      
ta
008      
230418s2023 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1038/s41408-023-00791-0 $2 doi
035    __
$a (PubMed)36737429
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Ogiya, Daisuke $u Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan
245    10
$a Identification of disease-related aberrantly spliced transcripts in myeloma and strategies to target these alterations by RNA-based therapeutics / $c D. Ogiya, Z. Chyra, SJ. Verselis, M. O'Keefe, J. Cobb, I. Abiatari, S. Talluri, AA. Sithara, T. Hideshima, MP. Chu, R. Hájek, DM. Dorfman, LM. Pilarski, KC. Anderson, S. Adamia
520    9_
$a Novel drug discoveries have shifted the treatment paradigms of most hematological malignancies, including multiple myeloma (MM). However, this plasma cell malignancy remains incurable, and novel therapies are therefore urgently needed. Whole-genome transcriptome analyses in a large cohort of MM patients demonstrated that alterations in pre-mRNA splicing (AS) are frequent in MM. This manuscript describes approaches to identify disease-specific alterations in MM and proposes RNA-based therapeutic strategies to eradicate such alterations. As a "proof of concept", we examined the causes of aberrant HMMR (Hyaluronan-mediated motility receptor) splicing in MM. We identified clusters of single nucleotide variations (SNVs) in the HMMR transcript where the altered splicing took place. Using bioinformatics tools, we predicted SNVs and splicing factors that potentially contribute to aberrant HMMR splicing. Based on bioinformatic analyses and validation studies, we provided the rationale for RNA-based therapeutic strategies to selectively inhibit altered HMMR splicing in MM. Since splicing is a hallmark of many cancers, strategies described herein for target identification and the design of RNA-based therapeutics that inhibit gene splicing can be applied not only to other genes in MM but also more broadly to other hematological malignancies and solid tumors as well.
650    _2
$a lidé $7 D006801
650    12
$a mnohočetný myelom $x genetika $x terapie $7 D009101
650    _2
$a alternativní sestřih $7 D017398
650    _2
$a RNA $7 D012313
650    _2
$a sestřih RNA $7 D012326
650    12
$a hematologické nádory $7 D019337
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Extramural $7 D052061
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Chyra, Zuzana $u Department of Hemato-oncology, University Hospital Ostrava, Ostrava, Czech Republic $u Department of Hemato-oncology, University of Ostrava, Ostrava, Czech Republic
700    1_
$a Verselis, Sigitas J $u Molecular Diagnostic Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA
700    1_
$a O'Keefe, Morgan $u Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
700    1_
$a Cobb, Jacquelyn $u Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
700    1_
$a Abiatari, Ivane $u Institute of Medical and Public Health Research, School of Medicine, Ilia State University, Tbilisi, Georgia
700    1_
$a Talluri, Srikanth $u Molecular Diagnostic Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA $u Veterans Administration Boston Healthcare System, West Roxbury, MA, USA
700    1_
$a Sithara, Anjana Anilkumar $u Department of Hemato-oncology, University Hospital Ostrava, Ostrava, Czech Republic $u Department of Hemato-oncology, University of Ostrava, Ostrava, Czech Republic
700    1_
$a Hideshima, Teru $u Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
700    1_
$a Chu, Michael P $u Department of Medicine, Department of Oncology, University of Alberta, Edmonton, AB, Canada
700    1_
$a Hájek, Roman $u Department of Hemato-oncology, University Hospital Ostrava, Ostrava, Czech Republic $u Department of Hemato-oncology, University of Ostrava, Ostrava, Czech Republic $1 https://orcid.org/0000000169556267 $7 nlk20000083645
700    1_
$a Dorfman, David M $u Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
700    1_
$a Pilarski, Linda M $u Department of Medicine, Department of Oncology, University of Alberta, Edmonton, AB, Canada
700    1_
$a Anderson, Kenneth C $u Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. kenneth_anderson@dfci.harvard.edu $1 https://orcid.org/0000000264180886
700    1_
$a Adamia, Sophia $u Jerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. sadamia@bidmc.harvard.edu $u Institute of Medical and Public Health Research, School of Medicine, Ilia State University, Tbilisi, Georgia. sadamia@bidmc.harvard.edu $u Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. sadamia@bidmc.harvard.edu $1 https://orcid.org/0000000157046040
773    0_
$w MED00187996 $t Blood cancer journal $x 2044-5385 $g Roč. 13, č. 1 (2023), s. 23
856    41
$u https://pubmed.ncbi.nlm.nih.gov/36737429 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20230418 $b ABA008
991    __
$a 20230425141232 $b ABA008
999    __
$a ok $b bmc $g 1924743 $s 1190463
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2023 $b 13 $c 1 $d 23 $e 20230203 $i 2044-5385 $m Blood cancer journal $n Blood Cancer J $x MED00187996
LZP    __
$a Pubmed-20230418

Najít záznam

Citační ukazatele

Možnosti archivace