Aldo Roccaro - Academia.edu (original) (raw)
Papers by Aldo Roccaro
Cancer Letters, 2015
Multiple myeloma (MM) is a type of B-cell malignancy that remains incurable to date. The bone mar... more Multiple myeloma (MM) is a type of B-cell malignancy that remains incurable to date. The bone marrow (BM) microenvironment plays a crucial role in MM progression. The chemokine SDF-1 (CXCL12) is an important actor of the BM microenvironment that has the ability to regulate numerous processes related to its malignant transformation during MM development. The activity of SDF-1 is mainly mediated by its specific receptor CXCR4, which is expressed at the surface of MM cells and various other BM cell types. Current treatments available for MM patients mainly target tumor cells but have limited effects on the BM microenvironment. In this context, SDF-1 and CXCR4 represent ideal targets for the normalization of the MM-supportive BM microenvironment. The present review focuses on the activity of SDF-1 in the MM BM microenvironment and the current efforts carried out to target the SDF-1/CXCR4 axis for treatment of MM.
Open Journal of Hematology, Feb 21, 2012
proteins in a reciprocal pro-survival loop. Such a bone marrow niche guarantees a survival advant... more proteins in a reciprocal pro-survival loop. Such a bone marrow niche guarantees a survival advantage for MM cells and has a crucial role in mediating drug resistance to chemotherapy agents. As the name suggests, hallmark characteristic of MM is the ability to localize in multiple, distant bone sites causing disruption of the normal bone architecture and impairment of normal hematopoiesis. The pathogenic mechanisms of MM rely then not only on proliferation of cancerous cells, but also on the ability of myeloma cells to traffic between sites and home to appropriate survival niches.
Open Journal of Hematology, Feb 21, 2012
proteins in a reciprocal pro-survival loop. Such a bone marrow niche guarantees a survival advant... more proteins in a reciprocal pro-survival loop. Such a bone marrow niche guarantees a survival advantage for MM cells and has a crucial role in mediating drug resistance to chemotherapy agents. As the name suggests, hallmark characteristic of MM is the ability to localize in multiple, distant bone sites causing disruption of the normal bone architecture and impairment of normal hematopoiesis. The pathogenic mechanisms of MM rely then not only on proliferation of cancerous cells, but also on the ability of myeloma cells to traffic between sites and home to appropriate survival niches.
Seminars in Hematology, 2011
microRNAs (miRNAs) are increasingly recognized as significant players in oncogenesis and tumor bi... more microRNAs (miRNAs) are increasingly recognized as significant players in oncogenesis and tumor biology through post-transcriptional gene regulation impacting broad pathways of proliferation, differentiation, apoptosis, metastasis, and cell survival. Recent studies have found abnormal expression of miRNAs in multiple myeloma (MM). Currently, the precise role of these miRNAs in the biology of MM remains to be elucidated, although they are predicted to be involved in plasma cell proliferation, survival, homing, or in MM cell interactions with the bone marrow microenvironment. Furthermore, a limited number of studies focusing on MM precursor disease (monoclonal gammopathy of undetermined significance [MGUS]) reveal significant differences in miRNA profiles between MGUS and normal plasma cells. Interestingly, several of the microRNAs differentially expressed in MGUS also show aberrant expression in MM, suggesting a role in early myelomagenesis. miRNA profiles can discriminate molecular subtypes of MM that are defined based on gene expression profiling (GEP) and cytogenetic abnormalities, demonstrating the potential diagnostic/ prognostic utility of miRNA profiling for subclassification of MM. Given the relative stability of miRNA and ability to isolate miRNA from routine clinical specimens, miRNA analysis promises to facilitate personalized diagnostics and therapies, and to provide insights into the biology of early myelomagenesis. Semin Hematol 48:39 -45.
Ash Annual Meeting Abstracts, Nov 20, 2009
Ash Annual Meeting Abstracts, Nov 16, 2012
Ash Annual Meeting Abstracts, Nov 16, 2012
Open Journal of Hematology, May 28, 2010
IgM monoclonal gammopathy in the serum. WM is considered an incurable disease, with an overall me... more IgM monoclonal gammopathy in the serum. WM is considered an incurable disease, with an overall median survival of only 5-6 years. The success of targeted therapy in multiple myeloma (MM) has led to the development and investigation of more than 30 new compounds in this disease and in other plasma cell dyscrasias WM, both in the preclinical settings and as part of clinical trials. Among therapeutical options, first-line therapies have been based on single-agent or combination regimens with alkylator agents, nucleoside analogues, and the monoclonal antibody anti-CD20. Based on the understanding of the complex interaction between tumor cells and bone marrow microenvironment and the signaling pathways that are deregulated in WM pathogenesis, a number of novel therapeutic agents are now available; and demonstrated significant efficacy in WM. The range of the ORR to these novel agents is between 25-80%. Ongoing and planned future clinical trials include those using PKC inhibitors such as enzastaurin, new proteasome inhibitors such as carfilzomib, histone deacetylase inhibitors such as LBH589, humanized CD20 antibodies such as Ofatumumab, and additional alkylating agents such as bendamustine. These agents, when compared to traditional chemotherapeutic agents, may lead in the future to higher responses, longer remissions and better quality of life for patients with WM. This review will mainly focus on those novel agent that entered clinical trial for the treatment of WM.
Open Journal of Hematology, May 28, 2010
IgM monoclonal gammopathy in the serum. WM is considered an incurable disease, with an overall me... more IgM monoclonal gammopathy in the serum. WM is considered an incurable disease, with an overall median survival of only 5-6 years. The success of targeted therapy in multiple myeloma (MM) has led to the development and investigation of more than 30 new compounds in this disease and in other plasma cell dyscrasias WM, both in the preclinical settings and as part of clinical trials. Among therapeutical options, first-line therapies have been based on single-agent or combination regimens with alkylator agents, nucleoside analogues, and the monoclonal antibody anti-CD20. Based on the understanding of the complex interaction between tumor cells and bone marrow microenvironment and the signaling pathways that are deregulated in WM pathogenesis, a number of novel therapeutic agents are now available; and demonstrated significant efficacy in WM. The range of the ORR to these novel agents is between 25-80%. Ongoing and planned future clinical trials include those using PKC inhibitors such as enzastaurin, new proteasome inhibitors such as carfilzomib, histone deacetylase inhibitors such as LBH589, humanized CD20 antibodies such as Ofatumumab, and additional alkylating agents such as bendamustine. These agents, when compared to traditional chemotherapeutic agents, may lead in the future to higher responses, longer remissions and better quality of life for patients with WM. This review will mainly focus on those novel agent that entered clinical trial for the treatment of WM.
The Journal of Molecular Diagnostics, 2015
The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the ... more The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the biology of disease. In this study, we found that the extracellular BM microenvironment in MM contains a unique miRNA signature detectable by miRNA microarray and quantitative real-time PCR, which is partially represented in the peripheral blood. Eleven miRNAs were significantly decreased in both BM and serum of MM patients in comparison with controls. Evaluation of these miRNAs in plasma of a separate cohort of MM patients and controls confirmed significantly aberrant levels of let-7a, let-7b, let-7i, miR-15b, miR-16, and miR-20a in both serum and plasma. We then studied the myeloma precursor diseases and found that a subset of the MM miRNAs exhibited aberrant expression in monoclonal gammopathy of undetermined significance and smoldering myeloma. miRNA analysis of enriched CD138(+) plasma cells from MM and monoclonal gammopathy of undetermined significance found that most of the validated MM BM signature miRNAs were significantly decreased in MM plasma cells. Gene expression profiling indicated that multiple targets of the decreased miRNAs found increased expression in MM plasma cells, including ATF2, HRAS, HDAC4, TGFB1, TGFBR1, and mitogen-activated protein kinases. The findings suggest that these miRNAs are detectable in aberrant levels in the peripheral blood of patients with plasma cell proliferation and may play a role in aberrant plasma cell proliferation and disease progression.
The Journal of Molecular Diagnostics, 2015
The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the ... more The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the biology of disease. In this study, we found that the extracellular BM microenvironment in MM contains a unique miRNA signature detectable by miRNA microarray and quantitative real-time PCR, which is partially represented in the peripheral blood. Eleven miRNAs were significantly decreased in both BM and serum of MM patients in comparison with controls. Evaluation of these miRNAs in plasma of a separate cohort of MM patients and controls confirmed significantly aberrant levels of let-7a, let-7b, let-7i, miR-15b, miR-16, and miR-20a in both serum and plasma. We then studied the myeloma precursor diseases and found that a subset of the MM miRNAs exhibited aberrant expression in monoclonal gammopathy of undetermined significance and smoldering myeloma. miRNA analysis of enriched CD138(+) plasma cells from MM and monoclonal gammopathy of undetermined significance found that most of the validated MM BM signature miRNAs were significantly decreased in MM plasma cells. Gene expression profiling indicated that multiple targets of the decreased miRNAs found increased expression in MM plasma cells, including ATF2, HRAS, HDAC4, TGFB1, TGFBR1, and mitogen-activated protein kinases. The findings suggest that these miRNAs are detectable in aberrant levels in the peripheral blood of patients with plasma cell proliferation and may play a role in aberrant plasma cell proliferation and disease progression.
Cell Reports, 2015
Extra-medullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis and resi... more Extra-medullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis and resistance to chemotherapy. However, molecular alterations that lead to EMD have not been well defined. We developed bone marrow (BM)- and EMD-prone MM syngeneic cell lines; identified that epithelial-to-mesenchymal transition (EMT) transcriptional patterns were significantly enriched in both clones compared to parental cells, together with higher levels of CXCR4 protein; and demonstrated that CXCR4 enhanced the acquisition of an EMT-like phenotype in MM cells with a phenotypic conversion for invasion, leading to higher bone metastasis and EMD dissemination in vivo. In contrast, CXCR4 silencing led to inhibited tumor growth and reduced survival. Ulocuplumab, a monoclonal anti-CXCR4 antibody, inhibited MM cell dissemination, supported by suppression of the CXCR4-driven EMT-like phenotype. These results suggest that targeting CXCR4 may act as a regulator of EMD through EMT-like transcriptional modulation, thus representing a potential therapeutic strategy to prevent MM disease progression.
Cell Reports, 2015
Extra-medullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis and resi... more Extra-medullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis and resistance to chemotherapy. However, molecular alterations that lead to EMD have not been well defined. We developed bone marrow (BM)- and EMD-prone MM syngeneic cell lines; identified that epithelial-to-mesenchymal transition (EMT) transcriptional patterns were significantly enriched in both clones compared to parental cells, together with higher levels of CXCR4 protein; and demonstrated that CXCR4 enhanced the acquisition of an EMT-like phenotype in MM cells with a phenotypic conversion for invasion, leading to higher bone metastasis and EMD dissemination in vivo. In contrast, CXCR4 silencing led to inhibited tumor growth and reduced survival. Ulocuplumab, a monoclonal anti-CXCR4 antibody, inhibited MM cell dissemination, supported by suppression of the CXCR4-driven EMT-like phenotype. These results suggest that targeting CXCR4 may act as a regulator of EMD through EMT-like transcriptional modulation, thus representing a potential therapeutic strategy to prevent MM disease progression.
British journal of haematology, 2015
Extramedullary disease (EMD), defined as an infiltrate of clonal plasma cells at an anatomic site... more Extramedullary disease (EMD), defined as an infiltrate of clonal plasma cells at an anatomic site distant from the bone marrow, is an uncommon manifestation of multiple myeloma. Six hundred and sixty-three consecutive patients with multiple myeloma who underwent stem cell transplantation between January 2005 and December 2011 were assessed for the presence of EMD. A cohort of 55 patients with biopsy-proven EMD was identified, comprising 8·3% of the total study population. EMD was present at the time of diagnosis in 14·5% of cases and at the time of relapse in 76% of patients. The most common EMD presentations at relapse were liver involvement and pleural effusions. EMD specimens had high expression of CD44 (92%) and moderate expression of CXCR4. The median overall survival from time of myeloma diagnosis was 4·1 years (95% CI: 3·1, 5·1) and the median overall survival from time of EMD diagnosis was 1·3 years (95% CI: 0·8, 2·3). This report demonstrates that the incidence of EMD has n...
Cancer Letters, 2015
Multiple myeloma (MM) is a type of B-cell malignancy that remains incurable to date. The bone mar... more Multiple myeloma (MM) is a type of B-cell malignancy that remains incurable to date. The bone marrow (BM) microenvironment plays a crucial role in MM progression. The chemokine SDF-1 (CXCL12) is an important actor of the BM microenvironment that has the ability to regulate numerous processes related to its malignant transformation during MM development. The activity of SDF-1 is mainly mediated by its specific receptor CXCR4, which is expressed at the surface of MM cells and various other BM cell types. Current treatments available for MM patients mainly target tumor cells but have limited effects on the BM microenvironment. In this context, SDF-1 and CXCR4 represent ideal targets for the normalization of the MM-supportive BM microenvironment. The present review focuses on the activity of SDF-1 in the MM BM microenvironment and the current efforts carried out to target the SDF-1/CXCR4 axis for treatment of MM.
Open Journal of Hematology, Feb 21, 2012
proteins in a reciprocal pro-survival loop. Such a bone marrow niche guarantees a survival advant... more proteins in a reciprocal pro-survival loop. Such a bone marrow niche guarantees a survival advantage for MM cells and has a crucial role in mediating drug resistance to chemotherapy agents. As the name suggests, hallmark characteristic of MM is the ability to localize in multiple, distant bone sites causing disruption of the normal bone architecture and impairment of normal hematopoiesis. The pathogenic mechanisms of MM rely then not only on proliferation of cancerous cells, but also on the ability of myeloma cells to traffic between sites and home to appropriate survival niches.
Open Journal of Hematology, Feb 21, 2012
proteins in a reciprocal pro-survival loop. Such a bone marrow niche guarantees a survival advant... more proteins in a reciprocal pro-survival loop. Such a bone marrow niche guarantees a survival advantage for MM cells and has a crucial role in mediating drug resistance to chemotherapy agents. As the name suggests, hallmark characteristic of MM is the ability to localize in multiple, distant bone sites causing disruption of the normal bone architecture and impairment of normal hematopoiesis. The pathogenic mechanisms of MM rely then not only on proliferation of cancerous cells, but also on the ability of myeloma cells to traffic between sites and home to appropriate survival niches.
Seminars in Hematology, 2011
microRNAs (miRNAs) are increasingly recognized as significant players in oncogenesis and tumor bi... more microRNAs (miRNAs) are increasingly recognized as significant players in oncogenesis and tumor biology through post-transcriptional gene regulation impacting broad pathways of proliferation, differentiation, apoptosis, metastasis, and cell survival. Recent studies have found abnormal expression of miRNAs in multiple myeloma (MM). Currently, the precise role of these miRNAs in the biology of MM remains to be elucidated, although they are predicted to be involved in plasma cell proliferation, survival, homing, or in MM cell interactions with the bone marrow microenvironment. Furthermore, a limited number of studies focusing on MM precursor disease (monoclonal gammopathy of undetermined significance [MGUS]) reveal significant differences in miRNA profiles between MGUS and normal plasma cells. Interestingly, several of the microRNAs differentially expressed in MGUS also show aberrant expression in MM, suggesting a role in early myelomagenesis. miRNA profiles can discriminate molecular subtypes of MM that are defined based on gene expression profiling (GEP) and cytogenetic abnormalities, demonstrating the potential diagnostic/ prognostic utility of miRNA profiling for subclassification of MM. Given the relative stability of miRNA and ability to isolate miRNA from routine clinical specimens, miRNA analysis promises to facilitate personalized diagnostics and therapies, and to provide insights into the biology of early myelomagenesis. Semin Hematol 48:39 -45.
Ash Annual Meeting Abstracts, Nov 20, 2009
Ash Annual Meeting Abstracts, Nov 16, 2012
Ash Annual Meeting Abstracts, Nov 16, 2012
Open Journal of Hematology, May 28, 2010
IgM monoclonal gammopathy in the serum. WM is considered an incurable disease, with an overall me... more IgM monoclonal gammopathy in the serum. WM is considered an incurable disease, with an overall median survival of only 5-6 years. The success of targeted therapy in multiple myeloma (MM) has led to the development and investigation of more than 30 new compounds in this disease and in other plasma cell dyscrasias WM, both in the preclinical settings and as part of clinical trials. Among therapeutical options, first-line therapies have been based on single-agent or combination regimens with alkylator agents, nucleoside analogues, and the monoclonal antibody anti-CD20. Based on the understanding of the complex interaction between tumor cells and bone marrow microenvironment and the signaling pathways that are deregulated in WM pathogenesis, a number of novel therapeutic agents are now available; and demonstrated significant efficacy in WM. The range of the ORR to these novel agents is between 25-80%. Ongoing and planned future clinical trials include those using PKC inhibitors such as enzastaurin, new proteasome inhibitors such as carfilzomib, histone deacetylase inhibitors such as LBH589, humanized CD20 antibodies such as Ofatumumab, and additional alkylating agents such as bendamustine. These agents, when compared to traditional chemotherapeutic agents, may lead in the future to higher responses, longer remissions and better quality of life for patients with WM. This review will mainly focus on those novel agent that entered clinical trial for the treatment of WM.
Open Journal of Hematology, May 28, 2010
IgM monoclonal gammopathy in the serum. WM is considered an incurable disease, with an overall me... more IgM monoclonal gammopathy in the serum. WM is considered an incurable disease, with an overall median survival of only 5-6 years. The success of targeted therapy in multiple myeloma (MM) has led to the development and investigation of more than 30 new compounds in this disease and in other plasma cell dyscrasias WM, both in the preclinical settings and as part of clinical trials. Among therapeutical options, first-line therapies have been based on single-agent or combination regimens with alkylator agents, nucleoside analogues, and the monoclonal antibody anti-CD20. Based on the understanding of the complex interaction between tumor cells and bone marrow microenvironment and the signaling pathways that are deregulated in WM pathogenesis, a number of novel therapeutic agents are now available; and demonstrated significant efficacy in WM. The range of the ORR to these novel agents is between 25-80%. Ongoing and planned future clinical trials include those using PKC inhibitors such as enzastaurin, new proteasome inhibitors such as carfilzomib, histone deacetylase inhibitors such as LBH589, humanized CD20 antibodies such as Ofatumumab, and additional alkylating agents such as bendamustine. These agents, when compared to traditional chemotherapeutic agents, may lead in the future to higher responses, longer remissions and better quality of life for patients with WM. This review will mainly focus on those novel agent that entered clinical trial for the treatment of WM.
The Journal of Molecular Diagnostics, 2015
The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the ... more The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the biology of disease. In this study, we found that the extracellular BM microenvironment in MM contains a unique miRNA signature detectable by miRNA microarray and quantitative real-time PCR, which is partially represented in the peripheral blood. Eleven miRNAs were significantly decreased in both BM and serum of MM patients in comparison with controls. Evaluation of these miRNAs in plasma of a separate cohort of MM patients and controls confirmed significantly aberrant levels of let-7a, let-7b, let-7i, miR-15b, miR-16, and miR-20a in both serum and plasma. We then studied the myeloma precursor diseases and found that a subset of the MM miRNAs exhibited aberrant expression in monoclonal gammopathy of undetermined significance and smoldering myeloma. miRNA analysis of enriched CD138(+) plasma cells from MM and monoclonal gammopathy of undetermined significance found that most of the validated MM BM signature miRNAs were significantly decreased in MM plasma cells. Gene expression profiling indicated that multiple targets of the decreased miRNAs found increased expression in MM plasma cells, including ATF2, HRAS, HDAC4, TGFB1, TGFBR1, and mitogen-activated protein kinases. The findings suggest that these miRNAs are detectable in aberrant levels in the peripheral blood of patients with plasma cell proliferation and may play a role in aberrant plasma cell proliferation and disease progression.
The Journal of Molecular Diagnostics, 2015
The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the ... more The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the biology of disease. In this study, we found that the extracellular BM microenvironment in MM contains a unique miRNA signature detectable by miRNA microarray and quantitative real-time PCR, which is partially represented in the peripheral blood. Eleven miRNAs were significantly decreased in both BM and serum of MM patients in comparison with controls. Evaluation of these miRNAs in plasma of a separate cohort of MM patients and controls confirmed significantly aberrant levels of let-7a, let-7b, let-7i, miR-15b, miR-16, and miR-20a in both serum and plasma. We then studied the myeloma precursor diseases and found that a subset of the MM miRNAs exhibited aberrant expression in monoclonal gammopathy of undetermined significance and smoldering myeloma. miRNA analysis of enriched CD138(+) plasma cells from MM and monoclonal gammopathy of undetermined significance found that most of the validated MM BM signature miRNAs were significantly decreased in MM plasma cells. Gene expression profiling indicated that multiple targets of the decreased miRNAs found increased expression in MM plasma cells, including ATF2, HRAS, HDAC4, TGFB1, TGFBR1, and mitogen-activated protein kinases. The findings suggest that these miRNAs are detectable in aberrant levels in the peripheral blood of patients with plasma cell proliferation and may play a role in aberrant plasma cell proliferation and disease progression.
Cell Reports, 2015
Extra-medullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis and resi... more Extra-medullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis and resistance to chemotherapy. However, molecular alterations that lead to EMD have not been well defined. We developed bone marrow (BM)- and EMD-prone MM syngeneic cell lines; identified that epithelial-to-mesenchymal transition (EMT) transcriptional patterns were significantly enriched in both clones compared to parental cells, together with higher levels of CXCR4 protein; and demonstrated that CXCR4 enhanced the acquisition of an EMT-like phenotype in MM cells with a phenotypic conversion for invasion, leading to higher bone metastasis and EMD dissemination in vivo. In contrast, CXCR4 silencing led to inhibited tumor growth and reduced survival. Ulocuplumab, a monoclonal anti-CXCR4 antibody, inhibited MM cell dissemination, supported by suppression of the CXCR4-driven EMT-like phenotype. These results suggest that targeting CXCR4 may act as a regulator of EMD through EMT-like transcriptional modulation, thus representing a potential therapeutic strategy to prevent MM disease progression.
Cell Reports, 2015
Extra-medullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis and resi... more Extra-medullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis and resistance to chemotherapy. However, molecular alterations that lead to EMD have not been well defined. We developed bone marrow (BM)- and EMD-prone MM syngeneic cell lines; identified that epithelial-to-mesenchymal transition (EMT) transcriptional patterns were significantly enriched in both clones compared to parental cells, together with higher levels of CXCR4 protein; and demonstrated that CXCR4 enhanced the acquisition of an EMT-like phenotype in MM cells with a phenotypic conversion for invasion, leading to higher bone metastasis and EMD dissemination in vivo. In contrast, CXCR4 silencing led to inhibited tumor growth and reduced survival. Ulocuplumab, a monoclonal anti-CXCR4 antibody, inhibited MM cell dissemination, supported by suppression of the CXCR4-driven EMT-like phenotype. These results suggest that targeting CXCR4 may act as a regulator of EMD through EMT-like transcriptional modulation, thus representing a potential therapeutic strategy to prevent MM disease progression.
British journal of haematology, 2015
Extramedullary disease (EMD), defined as an infiltrate of clonal plasma cells at an anatomic site... more Extramedullary disease (EMD), defined as an infiltrate of clonal plasma cells at an anatomic site distant from the bone marrow, is an uncommon manifestation of multiple myeloma. Six hundred and sixty-three consecutive patients with multiple myeloma who underwent stem cell transplantation between January 2005 and December 2011 were assessed for the presence of EMD. A cohort of 55 patients with biopsy-proven EMD was identified, comprising 8·3% of the total study population. EMD was present at the time of diagnosis in 14·5% of cases and at the time of relapse in 76% of patients. The most common EMD presentations at relapse were liver involvement and pleural effusions. EMD specimens had high expression of CD44 (92%) and moderate expression of CXCR4. The median overall survival from time of myeloma diagnosis was 4·1 years (95% CI: 3·1, 5·1) and the median overall survival from time of EMD diagnosis was 1·3 years (95% CI: 0·8, 2·3). This report demonstrates that the incidence of EMD has n...