Chromosome 1 abnormalities and survival of patients with multiple myeloma in the era of novel agents

Abstract Chromosome 1 abnormalities (C1As) are common genetic aberrations among patients with multiple myeloma (MM). We aimed to evaluate the significance of C1As among a contemporary cohort of patients with MM in the United States. We used electronic health records from the Flatiron Health database to select patients newly diagnosed with MM from January 2011 to March 2018 who were tested using fluorescence in situ hybridization within 90 days of diagnosis. We characterized patients as having documented C1As or other high-risk chromosomal abnormalities (HRCAs) as defined by the Revised-International Staging System (R-ISS) such as del(17p), t(14;16), and t(4;14). We used Kaplan-Meier methods to compare overall survival (OS) of patients with or without C1As and stratified log-rank tests (with the presence of HRCAs as a stratifying variable). We used Cox proportional hazards regression models to compare OS, adjusting for age, sex, stage, HRCAs, and type of first-line therapy. Of 3578 eligible patients, 844 (24%) had documented C1As. Compared with patients without C1As, patients with C1As were more likely to have higher stage (R-ISS stage III; 18% vs 12%), to have HRCAs (27% vs 14%), and to receive combinations of proteasome inhibitors and immunomodulatory agents (41% vs 34%). Median OS was lower for patients with C1As (46.6 vs 70.1 months; log-rank P < .001). C1As were independently associated with worse OS (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-2.69; P < .001), as were older age, higher R-ISS stage, HRCAs, and immunoglobulin A isotype. C1As were associated with inferior OS, independent of other HRCAs, despite greater use of novel therapies. Clinical trials testing newer therapies for high-risk MM should incorporate patients with C1As.

Download Full-text

Mortality of multiple myeloma diagnosed peri-hospitalization.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e20553 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e20553-e20553

Author(s):

Sam Rubinstein ◽

Elizabeth Sigworth ◽

Sandip Chaugai ◽

Qingxia M Chen ◽

Robert F. Cornell ◽

...

Keyword(s):

Multiple Myeloma ◽

Proportional Hazards ◽

Medical Center ◽

Staging System ◽

Outpatient Setting ◽

Cox Proportional Hazards ◽

Early Mortality ◽

Related Complication ◽

Exact Test ◽

Before And After

e20553 Background: Although modern therapeutics for multiple myeloma (MM) have resulted in improved overall survival (OS) in recent years, patients who present with an acute disease-related complication often have poor outcomes. We sought to compare the OS of patients diagnosed with MM in or shortly after hospitalization with those diagnosed in the outpatient setting. Methods: Patients treated for MM at Vanderbilt University Medical Center (VUMC) between 2000 and 2018 were included. OS was computed from date of diagnosis; patients still alive were censored at date last known alive or of last follow-up. Baseline laboratory and cytogenetic data were used to calculate Revised International Staging System (R-ISS) stage; age was also recorded. Dates of inpatient notes and encounter codes were identified and compared to date of diagnosis to identify patients diagnosed within 30 days of an inpatient stay; patients whose first encounter at VUMC was 30 days or more after their diagnosis date were excluded. Cox proportional hazards modeling was performed to investigate the effects of a diagnosis within 30 days of an inpatient encounter controlling for age and R-ISS on OS. Time-dependent coefficients were included to investigate the effects of a peri-hospitalization diagnosis on OS before and after 90 days. Mortality at 90 days for each group was compared using Fisher’s exact test. Results: A total of 681 patients were included, of whom 81 (11.8%) were diagnosed peri-hospitalization. Patients diagnosed peri-hospitalization had inferior OS within the first 90 days (adjusted HR 8.38, 95% CI 4.22-16.66, p < .001), but not after 90 days (Table). 90-day mortality for patients diagnosed peri-hospitalization was higher than for those not diagnosed peri-hospitalization (21.0% v. 3.3%, p < 0.001). Conclusions: Patients diagnosed with MM peri-hospitalization had high early mortality in this study, although patients surviving more than 90 days have similar mortality to those diagnosed as outpatients. Many factors could account for this finding, such as irreversible renal failure or immobility due to MM, hospital-related complications, or more aggressive MM phenotype. Predictive models of early mortality in MM should account for inpatient status at diagnosis. [Table: see text]

Download Full-text

Development and validation of a pediatric disease risk index for allogeneic hematopoietic cell transplantation.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.7503 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 7503-7503

Author(s):

Muna Qayed ◽

Carrie L Kitko ◽

Kwang Woo Ahn ◽

Mariam H Johnson ◽

Kirk R. Schultz ◽

...

Keyword(s):

High Risk ◽

Hematopoietic Cell Transplantation ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Disease Risk ◽

Risk Index ◽

Risk Groups ◽

The United States ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model

7503 Background: Characteristics such as disease, disease status and cytogenetic abnormalities impact relapse and survival after transplantation for acute myeloid (AML) and acute lymphoblastic (ALL) leukemia. In adults, these attributes were used to derive the disease risk index for survival. Thus, the current analysis sought to develop and validate a pediatric disease risk index (p-DRI). Methods: Eligible were patients aged <18 years with AML (n=1135) and ALL (n=1228) transplanted between 2008 and 2017 in the United States. Separate analyses were performed for AML and ALL. Patients were randomly assigned (1:1) to a training and validation cohort. Cox proportional hazards model with stepwise selection was used to select significant variables (2-sided p<0.05). The primary outcome was leukemia-free survival (LFS; relapse or death were events). Based on the magnitude of log(HR), a weighted score was assigned to each characteristic that met the level of significance and risk groups were created. Results: Four risk groups were identified for AML and three risk groups for ALL (Table). The 5-year probabilities of LFS for AML were 81% (68-91), 56% (51-61), 44% (39-49) and 21% (15-28) for good, intermediate, high and very high-risk groups, respectively. The 5-year probabilities of LFS for ALL were 68% (63-72), 50% (45-54) and 15% (3-34) for good, intermediate, high risk groups, respectively. Conclusions: This validated p-DRI successfully stratified children with AML and ALL for prognostication undergoing allogeneic transplantation. [Table: see text]

Download Full-text

Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group

Journal of Clinical Oncology ◽

10.1200/jco.2015.61.2267 ◽

2015 ◽

Vol 33 (26) ◽

pp. 2863-2869 ◽

Cited By ~ 641

Author(s):

Antonio Palumbo ◽

Hervé Avet-Loiseau ◽

Stefania Oliva ◽

Henk M. Lokhorst ◽

Hartmut Goldschmidt ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Chromosomal Abnormalities ◽

Laboratory Data ◽

Staging System ◽

Albumin Level ◽

Serum Lactate ◽

Serum Lactate Dehydrogenase ◽

Adaptive Partitioning ◽

International Staging System

Purpose The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Patients and Methods Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (less than the upper limit of normal range); R-ISS III (n = 295), including ISS stage III (serum β2-microglobulin level > 5.5 mg/L) and high-risk CA or high LDH level; and R-ISS II (n = 1,894), including all the other possible combinations. At a median follow-up of 46 months, the 5-year OS rate was 82% in the R-ISS I, 62% in the R-ISS II, and 40% in the R-ISS III groups; the 5-year PFS rates were 55%, 36%, and 24%, respectively. Conclusion The R-ISS is a simple and powerful prognostic staging system, and we recommend its use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival.

Download Full-text

A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1

Blood ◽

10.1182/blood-2006-07-038430 ◽

2006 ◽

Vol 109 (6) ◽

pp. 2276-2284 ◽

Cited By ~ 582

Author(s):

John D. Shaughnessy ◽

Fenghuang Zhan ◽

Bart E. Burington ◽

Yongsheng Huang ◽

Simona Colla ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Risk Score ◽

Staging System ◽

Therapeutic Interventions ◽

Chromosome 1 ◽

Chromosome 1P ◽

Chromosome 1Q ◽

Expression Of Genes ◽

High Risk Disease

Abstract To molecularly define high-risk disease, we performed microarray analysis on tumor cells from 532 newly diagnosed patients with multiple myeloma (MM) treated on 2 separate protocols. Using log-rank tests of expression quartiles, 70 genes, 30% mapping to chromosome 1 (P < .001), were linked to early disease-related death. Importantly, most up-regulated genes mapped to chromosome 1q, and down-regulated genes mapped to chromosome 1p. The ratio of mean expression levels of up-regulated to down-regulated genes defined a high-risk score present in 13% of patients with shorter durations of complete remission, event-free survival, and overall survival (training set: hazard ratio [HR], 5.16; P < .001; test cohort: HR, 4.75; P < .001). The high-risk score also was an independent predictor of outcome endpoints in multivariate analysis (P < .001) that included the International Staging System and high-risk translocations. In a comparison of paired baseline and relapse samples, the high-risk score frequency rose to 76% at relapse and predicted short postrelapse survival (P < .05). Multivariate discriminant analysis revealed that a 17-gene subset could predict outcome as well as the 70-gene model. Our data suggest that altered transcriptional regulation of genes mapping to chromosome 1 may contribute to disease progression, and that expression profiling can be used to identify high-risk disease and guide therapeutic interventions.

Download Full-text

Outcomes Among High Risk and Standard Risk Multiple Myeloma Patients Treated With High Dose Therapy and Autologous Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v122.21.3358.3358 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3358-3358

Author(s):

Maliha Nusrat ◽

Syed M. Kazmi ◽

Amanda Megan Cornelison ◽

Partow Kebriaei ◽

Yago Nieto ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

High Risk ◽

Chromosomal Abnormalities ◽

Poor Response ◽

Chromosome 1 ◽

High Dose ◽

Hematopoietic Stem ◽

Bone Marrow Plasma ◽

Standard Risk

Abstract Background Chromosomal analysis using conventional cytogenetics (CC) and interphase fluorescence in situ hybridization (FISH) identifies a high risk multiple myeloma population (HR-MM) characterized by poor response to chemotherapy and shorter survival. The objective of this study was to compare outcomes of autologous hematopoietic stem cell transplantation (ASCT) at our institution in HR-MM and standard risk MM (SR-MM) patients (pts) identified through CC and FISH. Methods Metaphase CC and FISH data was collected from medical records of MM pts who underwent ASCT at our institution between Jan 2005 to Dec 2009. HR-MM pts were defined if CC revealed deletion (del) of chromosome 13/13q, del17/17p, t(4;14), t(14;16), hypoploidy (<45 chromosomes excluding –Y), or chromosome 1 abnormalities [+1, -1, t(1;x)] in at least 2 metaphases; or if FISH showed del 17p, t(4;14). Kaplan & Meier method was used for assessing progression free survival (PFS) and overall survival (OS); log-rank test was used to evaluate the difference between pt groups and Cox proportional hazards models were fitted for multivariate analysis. Results Out of 670 MM pts who received ASCT during the specified time, 74 (11%) had HR-MM while 596 (89%) had SR-MM. Table 1 summarizes baseline characteristics and outcomes of HR- and SR-MM pts. In HR-MM pts, chromosome 1 aberrations were most common and seen in 53 (76%) pts while del13/13q, hypodiploidy, del17/17p and t(4;14) was found in 48 (65%), 27 (37%), 16 (22%) and 5 (9%) pts, respectively. Concurrence of high-risk chromosomal abnormalities (i.e. >1) occurred in 58% of HR-MM pts. As compared to SR-MM pts, HR-MM pts were more commonly male (72 vs. 56%), had a significantly higher bone marrow plasma cell burden at diagnosis (52 vs. 29%. p<0.001) or at time of ASCT (5 vs. 2%. p<0.000) and were refractory to treatment before undergoing ASCT (34 vs. 22%; p0.01). Melphalan 200mg/m2 was the most common conditioning regimen used and there was no difference in time to bone marrow engraftment and platelet recovery. With median follow up of 39.8 months after ASCT, HR-MM pts, as compared to SR-MM pts, had significantly lower rates of >/= PR (74 vs. 84%; p <0.01), median PFS (10.3 vs. 32.4 months p<0.001) and OS (28 vs. not reached, p<0.001). On multivariate analysis of the HR-MM pts, having only 1-high-risk cytogenetic abnormality or achieving at least very-good-partial-response (VGPR) after ASCT were factors independently associated with improved OS (p<0.002). In contrast, induction chemotherapy with bortezomib, myeloma status at time of ASCT and post-ASCT maintenance chemotherapy did not significantly affect PFS or OS. Conclusion HR-MM pts are characterized by higher bone marrow plasma cell burden, concurrence of high-risk chromosomal abnormalities, and poor response to induction or high dose chemotherapy followed by ASCT as compared to SR-MM pts. In HR-MM pts, having only 1-high risk cytogenetic abnormality or achieving at least VGPR with ASCT are independent factors associated with improved survival. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Prognostic Potential of Heart Rate and Hypertension in Multiple Myeloma Patients

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.681484 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jie Wang ◽

Manyun Tang ◽

Yunxiang Long ◽

Jingzhuo Song ◽

Limei Chen ◽

...

Keyword(s):

Multiple Myeloma ◽

Heart Rate ◽

Proportional Hazards ◽

Staging System ◽

Cox Proportional Hazards ◽

Chi Square ◽

Cox Proportional Hazards Models ◽

All Cause Mortality ◽

Chi Square Test ◽

International Staging System

Background: The prognosis of patients with multiple myeloma (MM) is variable and partly depends on their cardiovascular status. The presence of arrhythmias can lead to worse outcomes. Therefore, this study aimed to evaluate the potential of heart rate (HR) and hypertension in predicating the outcomes of MM patients.Methods: This study retrospectively enrolled patients with MM between January 1, 2010, and December 31, 2018, at the First Affiliated Hospital of Xi'an Jiaotong University. The endpoint was all-cause mortality. The Pearson's chi-square test was used to assess the association between hypertension and outcomes. Univariate and multivariate Cox proportional hazards models were developed to evaluate the relationship between HR and all-cause mortality.Results: A total of 386 patients were included. The mean HR was 83.8 ± 23.1 beats per minute (bpm). Patients with HR >100 bpm had a higher all-cause mortality (79.4%, 50/63) than those with 60 ≤ HR ≤ 100 bpm (39.9%, 110/276) and <60 bpm (19.1%, 9/47) (p < 0.001). Subgroup analysis based on the International Staging System and sex revealed similar relationships (p < 0.01). When stratified by age, patients with HR >100 bpm had higher all-cause mortality than those with a lower HR when age was <65 years or 65–75 years (p < 0.001) but not >75 years. The proportion of patients with hypertension was 54.7% (211/386). However, hypertension was not associated with all-cause mortality in MM patients (χ2=1.729, p > 0.05). MM patients with HR >100 bpm had the highest all-cause mortality.Conclusions: The prognostic potential of HR may be useful in aiding risk stratification and promoting the management of these patients.

Download Full-text

Epidemiology, Staging, and Management of Multiple Myeloma

Medical Sciences ◽

10.3390/medsci9010003 ◽

2021 ◽

Vol 9 (1) ◽

pp. 3

Author(s):

Sandeep Anand Padala ◽

Adam Barsouk ◽

Alexander Barsouk ◽

Prashanth Rawla ◽

Anusha Vakiti ◽

...

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

Bone Pain ◽

Western Europe ◽

Hematopoietic Cell Transplantation ◽

Chromosomal Abnormalities ◽

Proteasome Inhibitors ◽

Staging System ◽

Organ Damage ◽

The Us

Multiple myeloma (MM) is a plasma cell disorder that is on the rise throughout the world, especially in the US, Australia, and Western Europe. In the US, MM accounts for almost 2% of cancer diagnoses and over 2% of cancer deaths (more than double the global proportion). Incidence has risen by 126% globally and over 40% in the US since 1990, while global mortality has risen by 94% and US mortality has fallen by 18%. The 5 year survival in the US has more than doubled over the past decades with the introduction of new targeted therapies and transplant techniques. Risk factors for MM include age (average age of diagnosis is 69), race (African Americans are over double as likely to be diagnosed), sex (men are at a 1.5× risk), and family history. Diagnosis includes serum or urine electrophoresis and free light-chain assay but requires bone marrow biopsy. It is distinguished from smoldering myeloma and monoclonal gammopathy of undetermined significance by a high (>3 g/dL) level of M-protein (monoclonal light chains) and the presence of CRAB (Hypercalcemia, Renal failure, Anemia, Bone pain) symptoms, which include hypercalcemia, renal failure, anemia, and bone pain, suggesting an end-organ damage. International staging system staging involves beta 2 microglobulin and albumin levels, while the revised system considers prognostic factors such as lactate dehydrogenase levels and chromosomal abnormalities. Front-line management includes induction regimen, maintenance therapy and hematopoietic cell transplantation for eligible patients and bisphosphonates or bone-stimulating agents for the prevention of skeletal events. Treatment for relapsed disease includes newly approved monoclonal antibodies like the CD38-targeting daratumumab, proteasome inhibitors, immunomodulating agents, and investigational therapies such as B cell maturation antigen Chimeric antigen receptor T cells.

Download Full-text

The role of idecabtagene vicleucel in patients with heavily pretreated refractory multiple myeloma

Therapeutic Advances in Hematology ◽

10.1177/20406207211019622 ◽

2021 ◽

Vol 12 ◽

pp. 204062072110196

Author(s):

Albert Oriol ◽

Laura Abril ◽

Anna Torrent ◽

Gladys Ibarra ◽

Josep-Maria Ribera

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Safety Profile ◽

Proteasome Inhibitors ◽

Clinical Development ◽

Phase Iii ◽

Acceptable Safety Profile ◽

Refractory Multiple Myeloma ◽

High Risk Patients ◽

Risk Patients

The development of several treatment options over the last 2 decades has led to a notable improvement in the survival of patients with multiple myeloma. Despite these advances, the disease remains incurable for most patients. Moreover, standard combinations of alkylating agents, immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies targeting CD38 and corticoids are exhausted relatively fast in a proportion of high-risk patients. Such high-risk patients account for over 20% of cases and currently represent a major unmet medical need. The challenge of drug resistance requires the development of highly active new agents with a radically different mechanism of action. Several immunotherapeutic modalities, including antibody–drug conjugates and T-cell engagers, appear to be promising choices for patients who develop resistance to standard combinations. Chimeric antigen-receptor-modified T cells (CAR-Ts) targeting B-cell maturation antigen have demonstrated encouraging efficacy and an acceptable safety profile compared with alternative options. Multiple CAR-Ts are in early stages of clinical development, but the first phase III trials with CAR-Ts are ongoing for two of them. After the recent publication of the results of a phase II trial confirming a notable efficacy and acceptable safety profile, idecabtagene vicleucel is the first CAR-T to gain regulatory US Food and Drug Administration approval to treat refractory multiple myeloma patients who have already been exposed to antibodies against CD38, proteasome inhibitors, and immunomodulatory agents and who are refractory to the last therapy. Here, we will discuss the preclinical and clinical development of idecabtagene vicleucel and its future role in the changing treatment landscape of relapsed and refractory multiple myeloma.

Download Full-text

Suicide in prison and after release: a 17-year national cohort study

European Journal of Epidemiology ◽

10.1007/s10654-021-00782-0 ◽

2021 ◽

Author(s):

Anne Bukten ◽

Marianne Riksheim Stavseth

Keyword(s):

High Risk ◽

Cause Of Death ◽

Proportional Hazards ◽

Prison Population ◽

Cox Proportional Hazards ◽

Hazard Ratios ◽

Crude Mortality ◽

Icd 10 ◽

National Cohort ◽

National Register Data

Abstract Background People in prison have an extremely high risk of suicide. The aim of this paper is to describe all suicides in the Norwegian prison population from 2000 to 2016, during and following imprisonment; to investigate the timing of suicides; and to investigate the associations between risk of suicide and types of crime. Methods We used data from the Norwegian Prison Release study (nPRIS) including complete national register data from the Norwegian Prison Register and the Norwegian Cause of Death Register in the period 1.1.2000 to 31.12.2016, consisting of 96,856 individuals. All suicides were classified according to ICD-10 codes X60-X84. We calculated crude mortality rates (CMRs) per 100,000 person-years and used a Cox Proportional-Hazards regression model to investigate factors associated with suicide during imprisonment and after release reported as hazard ratios (HRs). Results Suicide accounted for about 10% of all deaths in the Norwegian prison population and was the leading cause of death in prison (53% of in deaths in prison). The CMR per 100,000 person years for in-prison suicides was 133.8 (CI 100.5–167.1) and was ten times higher (CMR = 1535.0, CI 397.9–2672.2) on day one of incarceration. Suicides after release (overall CMR = 82.8, CI 100.5–167.1) also peaked on day one after release (CMR = 665.7, CI 0–1419.1). Suicide in prison was strongly associated with convictions of homicide (HR 18.2, CI 6.5–50.8) and high-security prison level (HR 15.4, CI 3.6–65.0). Suicide after release was associated with convictions of homicide (HR 3.1, CI 1.7–5.5). Conclusion There is a high risk of suicide during the immediate first period of incarceration and after release. Convictions for severe violent crime, especially homicide, are associated with increased suicide risk, both in prison and after release.

Download Full-text

Whole-genome optical mapping of bone-marrow myeloma cells reveals association of extramedullary multiple myeloma with chromosome 1 abnormalities

Scientific Reports ◽

10.1038/s41598-021-93835-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eva Kriegova ◽

Regina Fillerova ◽

Jiri Minarik ◽

Jakub Savara ◽

Jirina Manakova ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

High Risk ◽

Copy Number ◽

Optical Mapping ◽

Chromosome 1 ◽

Gene Copy ◽

Whole Genome ◽

Myeloma Cells ◽

Genomic Architecture

AbstractExtramedullary disease (EMM) represents a rare, aggressive and mostly resistant phenotype of multiple myeloma (MM). EMM is frequently associated with high-risk cytogenetics, but their complex genomic architecture is largely unexplored. We used whole-genome optical mapping (Saphyr, Bionano Genomics) to analyse the genomic architecture of CD138+ cells isolated from bone-marrow aspirates from an unselected cohort of newly diagnosed patients with EMM (n = 4) and intramedullary MM (n = 7). Large intrachromosomal rearrangements (> 5 Mbp) within chromosome 1 were detected in all EMM samples. These rearrangements, predominantly deletions with/without inversions, encompassed hundreds of genes and led to changes in the gene copy number on large regions of chromosome 1. Compared with intramedullary MM, EMM was characterised by more deletions (size range of 500 bp–50 kbp) and fewer interchromosomal translocations, and two EMM samples had copy number loss in the 17p13 region. Widespread genomic heterogeneity and novel aberrations in the high-risk IGH/IGK/IGL, 8q24 and 13q14 regions were detected in individual patients but were not specific to EMM/MM. Our pilot study revealed an association of chromosome 1 abnormalities in bone marrow myeloma cells with extramedullary progression. Optical mapping showed the potential for refining the complex genomic architecture in MM and its phenotypes.

Download Full-text