Multiple Myeloma: Chromosome 1q+ cytogenetic abnormalities

Multiple copies of chromosome 1 (1q+) is a frequent CA in MM

MM is characterized by CAs in plasma cells¹
Frequent gains include 1q, 6p and 11q¹
1q+ is one of the most common CAs in MM

1q+ abnormalities are defined by copy number

Chromosome 1q abnormalities terminology³

+1q	Additional copies of any part of the long arm of chromosome 1 (1q), irrespective of copy number or DNA segment gained
Gain(1q)	Gain of only 1 extra copy of chromosome 1q (3 total copies)
Amp(1q)	“Amplification” of 1q, with 2 additional copies of chromosome 1q (4 or more total copies)

In MM, 1q+ is frequently denoted as 1q21+, which refers to a specific location – region 2, band 1 on the long arm of chromosome 1

Overexpression of certain genes in the 1q arm may drive pathogenesis and drug resistance^4,5

Key genes located in the 1q21 band: BCL9: Cell growth ILF2, ADAR: RNA metabolism MCL1: Anti-apoptosis CKS1B: Cell proliferation	Resistance to PIs through the upregulation of the proteasome genes, including PSMD⁶
PSMD4: Anti-PI

Other key genes outside of the 1q21 band include: SLAMF7, SLAMF3: Immunomodulatory receptors FCRH5, NEK2: Cell development CD1D: T-cell responses	Resistance to drugs that rely mainly on CDC through upregulation of complement inhibitors, such as CD55⁷
CD55, CD46: CDC inhibition

1q+ terminology when co-occurring with/without other high-risk cytogenetic abnormalities (HRCA)⁸

1q+ increases throughout the MM disease course^4,9

Prognosis worsens with increasing copy number

Incorporating 1q+ testing into clinical practice remains challenging

New staging systems, such as R2-ISS, MASS and R-ISS-1q,^12–14 are including gain/amp(1q), alongside other high-risk factors when defining disease stage, in order to refine predictions of clinical outcomes and highlight the prognostic impact of gain/amp(1q)

Although most guidelines include 1q+ in their HRCA definitions, the recommendations for FISH panel testing for 1q+ are inconsistent and there is little treatment guidance specific to gain/amp(1q)^15–17

IMWG guidelines include gain/amp(1q) in their definition of HRCAs, but do not include it as part of their recommended routine FISH panel¹⁵

Abbreviations

CA, cytogenetic abnormality; CDC, complement-dependent cytotoxicity; FISH, fluorescence in situ hybridization; HRCA, high-risk cytogenetic abnormality; IMWG, International Myeloma Working Group; ISS, international staging system; LDH, lactate dehydrogenase; MASS, The Mayo Additive Staging System; MM, multiple myeloma; MRD, minimal residual disease; NDMM, newly-diagnosed multiple myeloma; OS, overall survival; PFS, progression-free survival; PI, protease inhibitor; R-ISS, Revised International Staging System; RRMM, relapsed/refractory multiple myeloma.

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