Gain of Chromosome 1q is Associated with Early Progression in Multiple Myeloma Patients Treated with Lenalidomide, Bortezomib, and Dexamethasone

Schmidt, Timothy; Joseph, Nisha; Barwick, Benjamin G; Heffner, Leonard T.; Hofmeister, Craig C; Bernal, Leon; Dhodapkar, Madhav V.; Gupta, Vikas A.; Jaye, David L.; Boise, Lawrence H.; Lonial, Sagar; Nooka, Ajay K.; Kaufman, Jonathan L.

doi:10.1016/j.clml.2019.09.121

Cited by 6 publications

(4 citation statements)

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“…Chromosome 1 aberrations are very common in most hematologic malignancies and constitute the most common structural aberration in multiple myeloma (MM). [1][2][3][4][5][6] We have previously reported that chromosome 1 abnormalities such as gains and amplification of the long arm of the chromosome (1q21gain/amp), predicts a poor prognosis in MM. 1,3,7 Currently, abnormalities on chromosome 1 are not included in the widely adopted revised International Staging System (R-ISS) staging system.…”

Section: Introductionmentioning

confidence: 99%

Concomitant deletion of the short arm (del(1p13.3)) and amplification or gain (1q21) of chromosome 1 by fluorescence in situ hybridization are associated with a poor clinical outcome in multiple myeloma

Mohan

Gong²,

Ashby

et al. 2023

Cancer

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Background: Chromosome 1 abnormalities in multiple myeloma (MM) are increasingly recognized as high risk-defining features. The authors report the prognostic value of del(1p13.3) by fluorescence in situ hybridization (FISH) at enrollment in subjects treated on total therapy clinical trials 2-6.Methods: FISH probes were generated from specific BAC DNA clones for the AHCYL1 gene locus (1p13.3) and the CKS1B locus (1q21).Results: A total of 1133 patients were included in this analysis. Although del (1p13.3) was detected in 220 (19.4%) patients, 1q21gain or 1q21amp were observed in 300 (26.5%) and 150 (13.2%) patients, respectively. Concomitant del (1p13.3) with 1q21 gain or amp was observed in 65 (5.7%) and 29 (2.5%) patients, respectively. There was enrichment of high-risk features such as International Staging System (ISS) stage 3 disease and gene expression profiling (GEP)70 high risk (HR) in the group with del(1p13.3). Presence of del(1p13.3) confers inferior progression-free survival (PFS) and overall survival (OS). On multivariate analysis, the presence of ISS stage 3 disease, GEP70 HR, 1q21gain, and 1q21amp were independent predictors of PFS or OS. Conclusions:The PFS and OS of patients with combined abnormalities of del (1p13.3)/1q21gain or amp was significantly worse compared to del(1p13.3) alone and 1q21gain or 1q21 amp alone, which identifies a subset of patients with poor clinical outcomes.

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Section: Introductionmentioning

confidence: 99%

Concomitant deletion of the short arm (del(1p13.3)) and amplification or gain (1q21) of chromosome 1 by fluorescence in situ hybridization are associated with a poor clinical outcome in multiple myeloma

Mohan

Gong²,

Ashby

et al. 2023

Cancer

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“…This association with del 13q and high-risk cytogenetics has also been seen in previous studies and supported the basis for its adverse prognosis. 23 24…”

Section: Discussionmentioning

confidence: 99%

Cytogenetic Alterations and Correlation with Age and Gender in Patients of Multiple Myeloma: A Study from a Tertiary Care Center in Eastern India

Jha,

Saha,

Bhattacharyya

2024

South Asian J Cancer

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Background Multiple myeloma is a cytogenetically heterogeneous, evolving, and incurable disease. Differences in prevalence of myeloma already exist in Indian subcontinent as compared with Western world countries. This study attempts to investigate differences in incidence of cytogenetic abnormalities (CA) in Eastern Indian patients and study differences in incidence with respect to age and gender. Materials and Methods Interphase fluorescence in situ hybridization (FISH) was applied on purified plasma cells of 280 newly diagnosed myeloma cases using specific probes. Statistical Analysis Data was analyzed using SPSS software version 25. Results Note that 51.07% patients were FISH positive. Del13q was the most common CA. Significant association of del 13q with t(4;14), del 17p, and gain of 1q was seen. The frequencies of FISH positive and negative groups differed in the different age groups; higher number of cases in 41 to 50 years group in FISH positive group (p < 0.05) and lower number of cases in FISH positive group in 61 to 70 years (p < 0.05) as compared with FISH negative group. Del 17p had higher number of cases in age group 41 to 50 years and 51 to 60 years as compared with other age groups. Incidence of t(11;14) was in 5th to 7th decade while del 13q and t(4;14) had the widest range of age at presentation. Gender disparities were seen in high-risk cytogenetics like del 17p and 1q gain. Conclusion The differences in incidence rate of CAs per se in myeloma cases diagnosed in Indian subcontinent and the differences in incidence with respect to age and gender warrant further multicentric studies.

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“…The copy number gain of 1q21 (+1q21) is subclassified into gains (3 copies) and amplification (≥4 copies). Prognostically, 1q21 amplification is associated with a worse overall survival as compared to gain of 1q21 49 ( Fig. 2E ).…”

Section: Probe Selectionmentioning

confidence: 98%

“…Over expression of CKS1B was initially thought as the driver event, but later multiple genes such as MUC1 , MCL1 , ANP32E , BCL9 , PSMD4 , PDZK1 , NEK2 , ARNT , ILF2 , and ADAR1 have been known to play a role in progression. 49 50 51 52 53 54 Jumping translocations involving 1q is another known mechanism that results in gains of 1q. 53 The gain of 1q21 is considered as high risk as per the mSMART v 3.0 criteria and has been incorporated into the second revision of RISS.…”

Section: Probe Selectionmentioning

confidence: 99%

Role of Conventional Cytogenetics and FISH in the Laboratory Work Up of Plasma Cell Dyscrasias

Dhabe

Das

Parihar

2023

Indian J Med Paediatr Oncol

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Plasma cell dyscrasias are a heterogeneous group of neoplasms characterized by abnormal proliferation of plasma cells with or without over production of monoclonal immunoglobulins. Chromosomal abnormalities are acquired either early in the course of the disease or during disease progression. Plasma cell dyscrasias are categorized into multiple cytogenetic subtypes that form an integral component of risk-stratified treatment protocols. The primary genetic events are IgH gene translocations and non-random gains of chromosomes 3/5/7/9/11/15/19 and or 21. The secondary genetic events consist of chromosome 1 abnormalities (1p deletion and 1q gain or amplification), deletion 17p/TP53, deletion 13q, and MYC gene rearrangements. Plasma cells being at the end of differentiation spectrum of B cells, have low proliferative potential precluding the use of karyotyping in identification of chromosomal abnormalities. Analysis of enriched plasma cells using interphase fluorescent in situ hybridization (FISH) is the technique of choice for identifying these abnormalities. It is essential to enrich plasma cells before the FISH analysis, and numerous plasma cell enrichment techniques have been described. In the paper, we review the cytogenetic approach to identify clinically significant genetic aberrations including the effective use of FISH panels and plasma cell enrichment techniques.

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Gain of Chromosome 1q is Associated with Early Progression in Multiple Myeloma Patients Treated with Lenalidomide, Bortezomib, and Dexamethasone

Cited by 6 publications

References 0 publications

Concomitant deletion of the short arm (del(1p13.3)) and amplification or gain (1q21) of chromosome 1 by fluorescence in situ hybridization are associated with a poor clinical outcome in multiple myeloma

Concomitant deletion of the short arm (del(1p13.3)) and amplification or gain (1q21) of chromosome 1 by fluorescence in situ hybridization are associated with a poor clinical outcome in multiple myeloma

Cytogenetic Alterations and Correlation with Age and Gender in Patients of Multiple Myeloma: A Study from a Tertiary Care Center in Eastern India

Role of Conventional Cytogenetics and FISH in the Laboratory Work Up of Plasma Cell Dyscrasias

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