scholarly journals Disruption of IRElα through its Kinase Domain Attenuates Multiple Myeloma

2018 ◽  
Author(s):  
Jonathan M Harnoss ◽  
Adrien Le Thomas ◽  
Scot A Marsters ◽  
David A Lawrence ◽  
Min Lu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Transcription Factor ◽  
Small Molecule ◽  
Therapeutic Target ◽  
Plasma Cells ◽  
Critical Role ◽  
Kinase Domain ◽  
Kinase Inhibition

AbstractMultiple myeloma (MM) arises from malignant immunoglobulin-secreting plasma cells and remains an incurable, often lethal disease despite recent therapeutic advances. The unfolded-protein response sensor IRE1α supports protein secretion by deploying a kinase-endoribonuclease module to activate the transcription factor XBP1s. MM cells may coopt the IRE1α-XBP1s pathway; however, the validity of IRE1α as a potential MM therapeutic target is controversial. Here we show that genetic disruption of IRE1α or XBP1s, or pharmacologic IRE1α kinase inhibition, attenuated subcutaneous or orthometastatic growth of MM tumors in mice, and augmented efficacy of two well-established frontline antimyeloma agents, bortezomib or lenalidomide. Mechanistically, IRE1α perturbation inhibited expression of key components of the ER-associated degradation machinery, as well as cytokines and chemokines known to promote MM growth. Selective IRE1α kinase inhibition reduced viability of CD138+ plasma cells while sparing CD138− cells from bone marrow of newly diagnosed MM patients or patients whose disease relapsed after 1 - 4 lines of treatment in both US- and EU-based cohorts. IRE1α inhibition preserved survival and glucose-induced insulin secretion by pancreatic microislets. Together, these results establish a strong therapeutic rationale for targeting IRE1α with kinase-based small-molecule inhibitors in MM.Significance statementMultiple myeloma (MM) is a lethal malignancy of plasma cells. MM cells have an expanded endoplasmic reticulum (ER) that is constantly under stress due to immunoglobulin hyperproduction. The ER-resident sensor IRE1α mitigates ER stress by expanding the ER’s protein-folding capacity while supporting proteasomal degradation of misfolded ER proteins. IRE1α elaborates these functions by deploying its cytoplasmic kinase-RNase module to activate the transcription factor XBP1s. The validity of IRE1α as a potential therapeutic target in MM has been questioned. Using genetic and pharmacologic disruption in vitro and in vivo, we demonstrate that the IRE1α-XBP1s pathway plays a critical role in MM growth. We further show that IRE1α’s kinase domain is an effective and safe potential small-molecule target for MM therapy.

scholarly journals Disruption of IRE1α through its kinase domain attenuates multiple myeloma

2019 ◽  
Vol 116 (33) ◽  
pp. 16420-16429 ◽  
Author(s):  
Jonathan M. Harnoss ◽  
Adrien Le Thomas ◽  
Anna Shemorry ◽  
Scot A. Marsters ◽  
David A. Lawrence ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Kinase Domain ◽  
Primary Hepatocytes ◽  
Kinase Inhibition ◽  
Unfolded Protein ◽  
Cytokines And Chemokines ◽  
The Unfolded Protein Response ◽  
Protein Response

Multiple myeloma (MM) arises from malignant immunoglobulin (Ig)-secreting plasma cells and remains an incurable, often lethal disease despite therapeutic advances. The unfolded-protein response sensor IRE1α supports protein secretion by deploying a kinase–endoribonuclease module to activate the transcription factor XBP1s. MM cells may co-opt the IRE1α–XBP1s pathway; however, the validity of IRE1α as a potential MM therapeutic target is controversial. Genetic disruption of IRE1α or XBP1s, or pharmacologic IRE1α kinase inhibition, attenuated subcutaneous or orthometastatic growth of MM tumors in mice and augmented efficacy of two established frontline antimyeloma agents, bortezomib and lenalidomide. Mechanistically, IRE1α perturbation inhibited expression of key components of the endoplasmic reticulum-associated degradation machinery, as well as secretion of Ig light chains and of cytokines and chemokines known to promote MM growth. Selective IRE1α kinase inhibition reduced viability of CD138+ plasma cells while sparing CD138− cells derived from bone marrows of newly diagnosed or posttreatment-relapsed MM patients, in both US- and European Union-based cohorts. Effective IRE1α inhibition preserved glucose-induced insulin secretion by pancreatic microislets and viability of primary hepatocytes in vitro, as well as normal tissue homeostasis in mice. These results establish a strong rationale for developing kinase-directed inhibitors of IRE1α for MM therapy.

scholarly journals A Deptor Inhibitor Induces Its Degradation with Resulting Anti-Myeloma Cytotoxicity in Vitro and In Vivo

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1821-1821
Author(s):  
Mario I Vega ◽  
Yijiang Shi ◽  
Patrick Frost ◽  
Sara Huerta-Yepez ◽  
Alan Lichtenstein
Keyword(s):  
Multiple Myeloma ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Cytotoxic Effect ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Inhibition Of Proliferation ◽  
Induction Of Apoptosis

Multiple myeloma (MM) is a hematological disorder characterized by a proliferation of malignant monoclonal plasma cells in the bone marrow (BM) and / or in extramedullary sites. Despite recent progress in OS rates, MM remains an incurable disease and most patients will relapse and require treatment. Deptor is a component of mTOR complexes and a constitutive inhibitor of their activities. It is known that the inhibition of Deptor results in the inhibition of the proliferation and induction of apoptosis in MM cells. In addition, high levels of Deptor are predictive of a poor response to conventional therapies, indicating that Deptor expression are important as a prognostic marker for patients with myeloma and is a possible therapeutic target. Our group previously identified a drug which prevents mTOR-Deptor binding (NSC126405) and induces cellular cytotoxicity in MM (Shi Y, et al 2016). In this study, we developed a new related chemical inhibitor (43 M) capable of inducing the inhibition of the mTOR / Deptor interaction and results in the negative regulation of Deptor that leads to the inhibition of proliferation and induces apoptosis in several MM cell lines. The cytotoxic effect of 43 M is not dependent of caspase activation and induces the activation of p70 and AKT (T308). This leads to the induction of apoptosis in MM cell lines and tumor cells derived from MM patients. The degradation of Deptor induced by 43 M is dependent on the proteasome complex since it was prevented in the presence of MG132. In vivo, 43 M prevents the expression of Deptor in a xenograft tumor, and delayed tumor growth and interestingly, induces the eradication of tumors in 40% of mice in a murine model of MM, without significant toxic implications. Recent studies show that Deptor expression protects MM cells against Bortezomib treatment, suggesting that anti-Deptor drugs can synergize with proteasome inhibitors (PIs). However, the combination of 43 M + Bortezomib was not synergistic, and was antagonistic in vitro. These results are probably due to the prevention of the proteasomal degradation of Deptor, suggesting a possible use of the 43 M inhibitor in MM in the absence of the current PIs. This study describes for the first time the possible role of Deptor as a therapeutic target using a chemical inhibitor capable of degrading and inducing a cytotoxic effect in MM cell lines. In addition, Deptor is reported as an important therapeutic target in an in vivo MM model. Shi Y, Daniels-Wells TR, Frost P, Lee J, Finn RS, Bardeleben C, Penichet ML, Jung ME, Gera J, Lichtenstein A. Cytotoxic Properties of a DEPTOR-mTOR Inhibitor in Multiple Myeloma Cells. Cancer Res. 2016 Oct 1;76(19):5822-5831 Disclosures No relevant conflicts of interest to declare.

scholarly journals JAM-A as a Prognostic Factor and New Therapeutic Target in Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 307-307 ◽  
Author(s):  
Antonio Solimando ◽  
Andreas Brandl ◽  
Mattenheimer Katharina ◽  
Carolin Graf ◽  
Miriram Ritz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Healthy Subjects ◽  
Plasma Cells ◽  
Cell Membrane Protein ◽  
And Migration ◽  
Rpmi 8226

Abstract Cell adhesion in the multiple myeloma (MM) microenvironment is a mechanism by which MM plasma cells escape the effects of therapy and survive. To improve clinical strategies and overcome drug resistance, approaches directed to both MMPCs and bone marrow microenvironment are under investigation. Here, we examined the cell membrane protein Junctional adhesion molecule-A (JAM-A) as a clinical biomarker and novel therapeutic target for MM. We evaluated JAM-A expression by real time PCR (RT-PCR), flow cytometry and immunofluorescence microscopy in 132 MM patients at different stages and various MM cell lines. Next, we measured the concentrations of soluble JAM-A from MM and healthy subjects sera by enzyme linked immune assay (ELISA). We investigated JAM-A functionally in vitro and in vivo by transient gene silencing (siRNA) and with blocking antibodies. Patient-derived plasma cells (MMPCs) expressed increased JAM-A expression levels when compared to control PC from healthy individuals. Elevated JAM-A expression correlated with poor prognosis (Figure 1A,B). Furthermore, soluble JAM-A was significantly increased in MM patient sera when compared to healthy subjects. Additionally, MM cell lines showed high expression of both membrane and cytoplasmic JAM-A. Consequently, inhibition of JAM-A using specific siRNA treatment resulted in diminished tumorigenic potential, including decreased colony formation, chemotaxis and migration. Importantly, treatment of luciferase+RPMI-8226 MM bearing NSG with a JAM-A blocking monoclonal antibody reduced significantly MM progression and dissemination in vivo when compared to MM bearing mice that received an non-specific isotype control antibody (Figure 1C). Conclusively, our data suggest that JAM-A can serve as a biomarker of malignancy in MM patients. Soluble plasma JAM-A could contribute to serum-based clinical stratification. Furthermore, therapeutic targeting of JAM-A appears attractive for clinical translation. Figure 1 Figure 1. Disclosures Einsele: Celgene: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria.

scholarly journals Bioactive Compounds from Herbal Medicine Targeting Multiple Myeloma

2021 ◽  
Vol 11 (10) ◽  
pp. 4451
Author(s):  
Coralia Cotoraci ◽  
Alina Ciceu ◽  
Alciona Sasu ◽  
Eftimie Miutescu ◽  
Anca Hermenean
Keyword(s):  
Multiple Myeloma ◽  
Survival Rate ◽  
Plasma Cells ◽  
Inhibition Of Proliferation ◽  
In Vivo Experiments ◽  
Clonal Proliferation ◽  
Hematological Cancers ◽  
Monoclonal Proteins

Multiple myeloma (MM) is one of the most widespread hematological cancers. It is characterized by a clonal proliferation of malignant plasma cells in the bone marrow and by the overproduction of monoclonal proteins. In recent years, the survival rate of patients with multiple myeloma has increased significantly due to the use of transplanted stem cells and of the new therapeutic agents that have significantly increased the survival rate, but it still cannot be completely cured and therefore the development of new therapeutic products is needed. Moreover, many patients have various side effects and face the development of drug resistance to current therapies. The purpose of this review is to highlight the bioactive active compounds (flavonoids) and herbal extracts which target dysregulated signaling pathway in MM, assessed by in vitro and in vivo experiments or clinical studies, in order to explore their healing potential targeting multiple myeloma. Mechanistically, they demonstrated the ability to promote cell cycle blockage and apoptosis or autophagy in cancer cells, as well as inhibition of proliferation/migration/tumor progression, inhibition of angiogenesis in the tumor vascular network. Current research provides valuable new information about the ability of flavonoids to enhance the apoptotic effects of antineoplastic drugs, thus providing viable therapeutic options based on combining conventional and non-conventional therapies in MM therapeutic protocols.

EPCO-18. A MESENCHYMAL CELL POPULATION MEDIATES RESISTANCE TO AURORA KINASE INHIBITORS IN GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi5-vi5
Author(s):  
Robert Suter ◽  
Vasileios Stathias ◽  
Anna Jermakowicz ◽  
Hari Pradhyumnan ◽  
Maurizio Affer ◽  
...  
Keyword(s):  
Single Cell ◽  
Small Molecule ◽  
Kinase Inhibitor ◽  
Patient Survival ◽  
Aurora Kinase ◽  
Adult Brain ◽  
Sequencing Data ◽  
Kinase Inhibition

Abstract Glioblastoma (GBM) remains the most common adult brain cancer, with a dismal average patient survival of less than two years. No new treatments have been approved for GBM since the introduction of the alkylating agent temozolomide in 2005. Even then, temozolomide treatment only increases the average survival of GBM patients by a few months. Thus, novel therapeutic options are direly needed. The aurora kinases A and B are targetable and overexpressed in GBM, and their expression is highly correlated with patient survival outcomes. Our lab has found that small molecule aurora kinase inhibition reduces GBM tumor growth in vitro and in vivo, however, eventually tumors still grow. Computational analysis integrating compound transcriptional response signatures from the LINCS L1000 dataset with the single-cell RNA-sequencing data of patient GBM tumors resected at the University of Miami predicts that aurora inhibition targets a subset of cells present within any GBM tumor. Results of in vivo single-cell perturbation experiments with the aurora kinase inhibitor alisertib coincide with our predictions and reveal a cellular transcriptional phenotype resistant to aurora kinase inhibition, characterized by a mesenchymal expression program. We find that small molecules that are predicted to target different cell populations from alisertib, including this resistant mesenchymal population, synergize with alisertib to kill GBM cells. As a whole, we have identified the cellular population resistant to aurora kinase inhibition and have developed an analytical framework that identifies synergistic small molecule combinations by identifying compounds that target transcriptionally distinct cellular populations within GBM tumors.

scholarly journals IL-32 is a metabolic regulator promoting survival and proliferation of malignant plasma cells

2021 ◽  
Author(s):  
Kristin Roseth Aass ◽  
Robin Mjelle ◽  
Martin H. Kastnes ◽  
Synne S. Tryggestad ◽  
Luca M. van den Brink ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Oxidative Phosphorylation ◽  
Plasma Cells ◽  
Inflammatory Diseases ◽  
Mitochondrial Respiratory Chain ◽  
Gene Signature ◽  
Growth And Survival ◽  
Novel Concept

AbstractIL-32 is a non-classical cytokine expressed in cancers, inflammatory diseases and infections. IL-32 can have both extracellular and intracellular functions, and its receptor is not identified. We here demonstrate that endogenously expressed, intracellular IL-32 binds to components of the mitochondrial respiratory chain and promotes oxidative phosphorylation. Knocking out IL-32 in malignant plasma cells significantly reduced survival and proliferation in vitro and in vivo. High throughput transcriptomic and MS-metabolomic profiling of IL-32 KO cells revealed that loss of IL-32 leads to profound perturbations in metabolic pathways, with accumulation of lipids, pyruvate precursors and citrate, indicative of reduced mitochondrial function. IL-32 is expressed in a subgroup of multiple myeloma patients with an inferior prognosis. Primary myeloma cells expressing IL-32 were characterized by a plasma cell gene signature associated with immune activation, proliferation and oxidative phosphorylation. We propose a novel concept for regulation of metabolism by an intracellular cytokine and identify IL-32 as an endogenous growth and survival factor for malignant plasma cells. IL-32 is a potential prognostic biomarker and a treatment target in multiple myeloma.

scholarly journals Global Genomic Analysis of Newly Diagnosed t(4 ;14) Multiple Myeloma Reveals a Specific Mutational Spectrum and Identifies PKD2 As a Potential Therapeutic Target

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4462-4462
Author(s):  
Xiu Ly Song ◽  
Raphaël Szalat ◽  
Alexis Talbot ◽  
HaiVu Nguyen ◽  
Mehmet K. Samur ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Plasma Cells ◽  
Genomic Analysis ◽  
Sequencing Analysis ◽  
Newly Diagnosed ◽  
Potential Therapeutic Target ◽  
Mutational Landscape

Abstract In Multiple Myeloma (MM), the t(4;14) translocation is associated with a poor outcome. However, beside this translocation, the genetic events which determine the adverse evolution of the disease and the resistance to treatments remain elusive. In this study we performed whole exome or RNA sequencing analysis of samples from 65 newly diagnosed t(4;14) MM. We found that NRAS, KRAS, MAPK and FGFR3 are frequently mutated (12%, 9%, 13.8%, and 20% respectively). Overall, the FGFR3/RAS/BRAF/MAPK genes were mutated in 36 cases (54%). There was a negative correlation between mutations in FGFR3 and those occurring in NRAS, KRAS and BRAF as expected from the mutually exclusive occurrence of mutations in these genes. In addition to alterations in TP53 and DIS3, we found marked elevated frequency of mutations in PRKD2 (10.7%), ATM/ATR (10.7%) and MYCBP2 (7.6%), reduced frequency in FAM46C (1.5%) and no mutation in TRAF3 and CCND1. Mutations in ATM/ATR were strongly associated with the MB4-2 breakpoint (Bp) (p = 1.62 10-4) and significantly correlated with mutations affecting genes coding for members of the MAPK family. We observed a positive correlation between non-silent mutations in PRKD2 and the MB4-1 or MB4-3 Bp (p = 1.3 10-2). Of note, PRKD2 mutations are exclusively found in 3 t(4;14) MM cell lines and among the 84 MM sequenced by Bolli et al. (1), none of the non t(4;14) patient were mutated in PRKD2, indicating that this genetic lesion is associated with t(4;14) MM. In the NCI-H929 t(4;14) MM cell line, which is mutated for PRKD2, encoding the PKD2 serine/threonine kinase, we observed elevated levels of phosphorylated PKD2. Furthermore, inhibition of PKD, decreased PKD2 phosphorylation and triggered reduced proliferation and apoptosis of MM cell lines and fresh plasma cells from patients in vitro. These results define a specific mutational landscape for t(4;14) MM and identify PKD2 as a potential therapeutic target in MM patients. Altogether, these results define a specific mutational landscape for t(4;14) MM and identify PKD2 as a potential therapeutic target in MM patients. Reference 1. Bolli, N., Avet-Loiseau, H., Wedge, D.C., Van Loo, P., Alexandrov, L.B., Martincorena, I., Dawson, K.J., Iorio, F., Nik-Zainal, S., Bignell, G.R., et al. (2014). Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat Commun 5, 2997. Disclosures Munshi: Janssen: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Merck: Consultancy; Pfizer: Consultancy; Oncopep: Patents & Royalties.

scholarly journals A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo

Leukemia ◽  
2016 ◽  
Vol 31 (8) ◽  
pp. 1743-1751 ◽  
Author(s):  
S Hipp ◽  
Y-T Tai ◽  
D Blanset ◽  
P Deegen ◽  
J Wahl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
T Cell ◽  
Plasma Cells ◽  
Ex Vivo ◽  
Xenograft Model ◽  
Selective Lysis ◽  
Bispecific T Cell Engager

Abstract B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein that is expressed on malignant plasma cells of multiple myeloma (MM) patients and therefore is an ideal target for T-cell redirecting therapies. We developed a bispecific T-cell engager (BiTE) targeting BCMA and CD3ɛ (BI 836909) and studied its therapeutic impacts on MM. BI 836909 induced selective lysis of BCMA-positive MM cells, activation of T cells, release of cytokines and T-cell proliferation; whereas BCMA-negative cells were not affected. Activity of BI 836909 was not influenced by the presence of bone marrow stromal cells, soluble BCMA or a proliferation-inducing ligand (APRIL). In ex vivo assays, BI 836909 induced potent autologous MM cell lysis in both, newly diagnosed and relapsed/refractory patient samples. In mouse xenograft studies, BI 836909 induced tumor cell depletion in a subcutaneous NCI-H929 xenograft model and prolonged survival in an orthotopic L-363 xenograft model. In a cynomolgus monkey study, administration of BI 836909 led to depletion of BCMA-positive plasma cells in the bone marrow. Taken together, these results show that BI 836909 is a highly potent and efficacious approach to selectively deplete BCMA-positive MM cells and represents a novel immunotherapeutic for the treatment of MM.

scholarly journals Kinesin Motor Protein KIFC1 Is a Target Protein of miR-338-3p and Is Associated With Poor Prognosis and Progression of Renal Cell Carcinoma

2018 ◽  
Vol 27 (1) ◽  
pp. 125-137 ◽  
Author(s):  
Gang Li ◽  
Tie Chong ◽  
Jie Yang ◽  
Hongliang Li ◽  
Haiwen Chen
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Therapeutic Target ◽  
Renal Cell ◽  
Critical Role ◽  
Survival Prognosis ◽  
Inhibition Of Proliferation ◽  
Invasion And Migration

KIFC1 (kinesin family member C1) plays a critical role in clustering of extra centrosomes in various cancer cells and thus could be considered as a promising therapeutic target. However, whether KIFC1 is involved in the procession of renal cell carcinoma (RCC) still remains unclear. In this study, we found that KIFC1 was upregulated in RCC tissues and is responsible for RCC tumorigenesis (p < 0.001). The high expression of KIFC1 correlates with aggressive clinicopathologic parameters. Kaplan‐Meier analysis suggested that KIFC1 was associated with poor survival prognosis in RCC. Silencing KIFC1 dramatically resulted in inhibition of proliferation, delayed the cell cycle at G2/M phase, and suppressed cell invasion and migration in vitro. The antiproliferative effect of KIFC1 silencing was also observed in xenografted tumors in vivo. miR-338-3p could directly bind to the 3′-untranslated region (3′-UTR) of KIFC1, and ectopic miR-338-3p expression mimicked the inhibitory functions of KIFC1 silencing on RCC cells through inactivation of the PI3K/AKT signaling pathway. Therefore, these results revealed that KIFC1 may be a novel biomarker and an effective therapeutic target for the treatment of RCC.

scholarly journals Characterization of Nonrandom Chromosomal Gains and Losses in Multiple Myeloma by Comparative Genomic Hybridization

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 3007-3010 ◽  
Author(s):  
Juan C. Cigudosa ◽  
Pulivarthi H. Rao ◽  
M. Jose Calasanz ◽  
M. Dolores Odero ◽  
Joseph Michaeli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Comparative Genomic Hybridization ◽  
Plasma Cells ◽  
Comparative Genomic ◽  
Genomic Hybridization ◽  
Banding Analysis ◽  
Chromosomal Changes ◽  
Gains And Losses

Clonal chromosomal changes in multiple myeloma (MM) and related disorders are not well defined, mainly due to the low in vivo and in vitro mitotic index of plasma cells. This difficulty can be overcome by using comparative genomic hybridization (CGH), a DNA-based technique that gives information about chromosomal copy number changes in tumors. We have performed CGH on 25 cases of MM, 4 cases of monoclonal gammopathy of uncertain significance, and 1 case of Waldenstrom's macroglobulinemia. G-banding analysis of the same group of patients demonstrated clonal chromosomal changes in only 13 (43%), whereas by CGH, the number of cases with clonal chromosomal gains and losses increased to 21 (70%). The most common recurrent changes detected by CGH were gain of chromosome 19 or 19p and complete or partial deletions of chromosome 13. +19, an anomaly that has so far not been detected as primary or recurrent change by G-banding analysis of these tumors, was noted in 2 cases as a unique change. Other recurrent changes included gains of 9q, 11q, 12q, 15q, 17q, and 22q and losses of 6q and 16q. We have been able to narrow the commonly deleted regions on 6q and 13q to bands 6q21 and 13q14-21. Gain of 11q and deletion of 13q, which have previously been associated with poor outcome, can thus be detected by CGH, allowing the use of this technique for prognostic evaluation of patients, without relying on the success of conventional cytogenetic analysis.

Sign in / Sign up

Export Citation Format

Share Document