Fluorescence in situ hybridization analysis of aneuploidization patterns in monoclonal gammopathy of undetermined significance versus multiple myeloma and plasma cell leukemia

Rasillo, Ana; Dolores, Tabernero María; Luz, Sánchez María; Martín, Pérez de Andrés; Marta, Martín Ayuso; Hernández, José; Jesús, Moro María; Javier, Fernández-Calvo; María, Sayagués José; Bortoluci, A. M.; Miguel, Jesús F. San; Órfão, Alberto

doi:10.1002/cncr.11100

Cited by 35 publications

(3 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It follows that MGUS, despite being a clinically indolent condition for most patients, can show a rather unexpected degree of clonal heterogeneity with some founder lesions and others acquired during disease course. This may serve as a "catalogue" of genomic lesions that provide the seed for further disease progression upon acquisition of a subsequent hit, 20,[66][67][68][69][70][71]73,75,76 recapitulating the "big-bang theory" originally described in solid cancers. 11,50,73 Disease evolution: From MGUS to smoldering MM and symptomatic phase…”

Section: Genomic Features Driving Mgus Developmentmentioning

confidence: 99%

A Journey Through Myeloma Evolution: From the Normal Plasma Cell to Disease Complexity

et al. 2020

View full text Add to dashboard Cite

The knowledge of cancer origin and the subsequent tracking of disease evolution represent unmet needs that will soon be within clinical reach. This will provide the opportunity to improve patient's stratification and to personalize treatments based on cancer biology along its life history. In this review, we focus on the molecular pathogenesis of multiple myeloma (MM), a hematologic malignancy with a well-known multi-stage disease course, where such approach can sooner translate into a clinical benefit. We describe novel insights into modes and timing of disease initiation. We dissect the biology of the preclinical and pre-malignant phases, elucidating how knowledge of the genomics of the disease and the composition of the microenvironment allow stratification of patients based on risk of disease progression. Then, we explore cell-intrinsic and cell-extrinsic drivers of MM evolution to symptomatic disease. Finally, we discuss how this may relate to the development of refractory disease after treatment. By integrating an evolutionary view of myeloma biology with the recent acquisitions on its clonal heterogeneity, we envision a way to drive the clinical management of the disease based on its detailed biological features more than surrogates of disease burden.

show abstract

Section: Genomic Features Driving Mgus Developmentmentioning

confidence: 99%

A Journey Through Myeloma Evolution: From the Normal Plasma Cell to Disease Complexity

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Recent data suggest that the acquisition of the hyperdiploid state is a stepwise process, which begins at the early stages of the disease development [ 61 , 79 , 478 ]. Plasma cells in most patients with MGUS carry numerical abnormalities of at least one of chromosomes (most often 6, 9, 13, 15, 17, 19), and up to ~50% are classified as hyperdiploid [ 57 , 478 , 480 , 481 ]. More chromosomes are gained as the disease progresses, and some patients acquire whole-genome duplications at the extreme end of the disease evolution [ 61 , 478 ].…”

Section: Structural Variations In the MM Genomesmentioning

confidence: 99%

Genome Instability in Multiple Myeloma: Facts and Factors

Aksenova

Zhuk

Lada

et al. 2021

Cancers

View full text Add to dashboard Cite

Multiple myeloma (MM) is a malignant neoplasm of terminally differentiated immunoglobulin-producing B lymphocytes called plasma cells. MM is the second most common hematologic malignancy, and it poses a heavy economic and social burden because it remains incurable and confers a profound disability to patients. Despite current progress in MM treatment, the disease invariably recurs, even after the transplantation of autologous hematopoietic stem cells (ASCT). Biological processes leading to a pathological myeloma clone and the mechanisms of further evolution of the disease are far from complete understanding. Genetically, MM is a complex disease that demonstrates a high level of heterogeneity. Myeloma genomes carry numerous genetic changes, including structural genome variations and chromosomal gains and losses, and these changes occur in combinations with point mutations affecting various cellular pathways, including genome maintenance. MM genome instability in its extreme is manifested in mutation kataegis and complex genomic rearrangements: chromothripsis, templated insertions, and chromoplexy. Chemotherapeutic agents used to treat MM add another level of complexity because many of them exacerbate genome instability. Genome abnormalities are driver events and deciphering their mechanisms will help understand the causes of MM and play a pivotal role in developing new therapies.

show abstract

“…The confirmation of the genetic aberration of 1q21, using a sequence-specific DNA probe for 1q21/CKS1B (Jinpujia Medical Co., Ltd., Beijing, China, F04008R-00), was analyzed by Kindstar Global Technology, China. The specific steps were done according to the protocol outlined in previous studies (14)(15)(16). Under the excitation of the red monochromatic filter, the fluorescence hybridization signal of the cells was observed with the Olympus BX51 fluorescence microscope (Olympus, Japan).…”

Section: Interphase Fluorescence In Situ Hybridizationmentioning

confidence: 99%

Globular C1q Receptor (gC1qR/p32/HABP1) Suppresses the Tumor-Inhibiting Role of C1q and Promotes Tumor Proliferation in 1q21-Amplified Multiple Myeloma

Sun

Jiang

et al. 2020

Front. Immunol.

View full text Add to dashboard Cite

Immunodeficiencies are widely becoming known as important features of multiple myeloma (MM) and may promote the proliferation of malignant cells as well as confer resistance to therapy. Few studies focus on the immunomodulatory effects of the complement system on MM. This study aims to explore the role of C1q in MM patients. Plasma C1q was found to be significantly reduced in MM patients, and the amount of C1q deposited around the CD138 + cells in bone marrow (BM) biopsy sections was observed to be much higher, especially in the subgroup with 1q21 amplification (Amp1q21). CD138 + cells expressed higher levels of C1q receptors (C1qRs) than CD138 − cells. Patients with Amp1q21 expressed higher levels of globular C1qR (gC1qR), whereas patients without Amp21 expressed higher levels of collagen tail C1qR (cC1qR). Additionally, gC1qR was noted to suppress the MM-inhibiting role of C1q in H929, U266, and MM1S. gC1qR interacts with insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), which also suppressed the function of C1q and regulated CDC28 protein kinase regulatory subunit 1B (CKS1B) mRNA. In summary, gC1qR suppressed the MM-inhibiting role of C1q and regulated CKS1B mRNA in promoting tumor proliferation via IGF2BP3 in 1q21-amplified MM. Our findings provide novel evidence on how MM cells evade the immune system and promote survival as well as suggest possible novel targets for future therapies of MM.

show abstract

Fluorescence in situ hybridization analysis of aneuploidization patterns in monoclonal gammopathy of undetermined significance versus multiple myeloma and plasma cell leukemia

Cited by 35 publications

References 38 publications

A Journey Through Myeloma Evolution: From the Normal Plasma Cell to Disease Complexity

A Journey Through Myeloma Evolution: From the Normal Plasma Cell to Disease Complexity

Genome Instability in Multiple Myeloma: Facts and Factors

Globular C1q Receptor (gC1qR/p32/HABP1) Suppresses the Tumor-Inhibiting Role of C1q and Promotes Tumor Proliferation in 1q21-Amplified Multiple Myeloma

Contact Info

Product

Resources

About