Zhou Ping, Mansukhani Mahesh M, Yeh Raymond, Lu Jiesheng, Xia Hongai, Koganti Lahari, Pang Jiuhong, Toskic Denis, Scalia Stephanie, Ma Xun, Lee Lisa X, Wong Sandy W, Chung Alfred, Tuchman Sascha A, Fogaren Terry, Coady Lyons Nancy, Varga Cindy, Lentzsch Suzanne, Comenzo Raymond L
The Tufts Medicine Myeloma and Amyloid Program, Tufts Medical Center, 800 Washington Street, P.O. Box 826, Boston, MA 02111, USA.
Columbia University Laboratory of Personalized Genomic Medicine, Department of Pathology & Cell Biology, Columbia University Irving Medical Center (CUIMC), New York, NY 10032, USA.
J Clin Med. 2025 Jun 11;14(12):4146. doi: 10.3390/jcm14124146.
To reduce the early mortality of light-chain amyloidosis (AL), earlier diagnosis is needed. To pursue this goal, we conducted a multicenter study screening for AL λ-type (NCT04615572) in subjects > 60 years of age with λ smoldering myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS), a light-chain differential (dFLC, λ minus κ) > 23 mg/L, and no prior amyloid diagnosis. : Variables included AL-related IGVL gene usage and clonal plasma cell cytogenetic abnormalities, such as t(11;14) or gain 1q, which are present in 75% of AL cases. Here, 9 out of 33 λ IGVL genes, accounting for 90% of AL λ cases, were considered to be AL-related. Bone marrow was obtained, plasma cell cytogenetics and next generation sequencing for IGVL genes were performed, and subjects with AL-related IGVL genes were screened for AL using tissue studies. : From 2021 to 2023, we enrolled 30 subjects (19 M/11 F) with a median age of 68.5 years old (IQR 64.3-73), 17 SMM and 13 MGUS, with a median of 6% marrow plasma cells (range, 3.5-40). Here, 11 SMM and 4 MGUS cases had t(11;14) or gain 1q; 10/17 SMM and 12/13 MGUS had AL-related genes, and AL was ultimately confirmed by tissue biopsy in 3 with SMM. SMM, AL-related IGVL genes, and t(11;14) or gain 1q were found in 6 SMM subjects, including the 3 with AL (3/6 vs. 0/16; < 0.05, Fisher's exact, two-tailed). : These results justify a larger study screening for AL in SMM to develop a likelihood algorithm for AL using dFLC, IGVL gene usage, and the presence of t(11;14) or gain 1q.
为降低轻链淀粉样变性（AL）的早期死亡率，需要更早进行诊断。为实现这一目标，我们开展了一项多中心研究，对年龄大于60岁、患有λ冒烟型骨髓瘤（SMM）或意义未明的单克隆丙种球蛋白病（MGUS）、轻链差值（dFLC，λ减去κ）>23mg/L且既往无淀粉样变性诊断的受试者进行AL λ型筛查（NCT04615572）。变量包括与AL相关的IGVL基因使用情况和克隆性浆细胞细胞遗传学异常，如t(11;14)或1q增益，这些在75%的AL病例中存在。在此，33个λ IGVL基因中的9个，占AL λ病例的90%，被认为与AL相关。获取骨髓，进行浆细胞细胞遗传学检查和IGVL基因的下一代测序，并使用组织研究对具有与AL相关IGVL基因的受试者进行AL筛查。从2021年到2023年，我们纳入了30名受试者（19名男性/11名女性），中位年龄为68.5岁（四分位间距64.3 - 73），17例SMM和13例MGUS，中位骨髓浆细胞比例为6%（范围3.5 - 40）。在此，11例SMM和4例MGUS病例有t(11;14)或1q增益；10/17例SMM和12/13例MGUS有与AL相关的基因，最终3例SMM通过组织活检确诊为AL。在6例SMM受试者中发现了SMM、与AL相关的IGVL基因以及t(11;14)或1q增益，其中包括3例患有AL的受试者（3/6 vs. 0/16；<0.05，Fisher精确检验，双侧）。这些结果证明有必要开展一项更大规模的研究，对SMM进行AL筛查，以利用dFLC、IGVL基因使用情况以及t(11;14)或1q增益的存在情况制定AL的可能性算法。
