Do myeloproliferative neoplasms and multiple myeloma share the same genetic susceptibility loci?

Abstract

Myeloproliferative neoplasms (MPNs) are a group of diseases that cause myeloid hematopoietic cells to overproliferate. Epidemiological and familial studies suggest that genetic factors contribute to the risk of developing MPN, but the genetic susceptibility of MPN is still not well known. Indeed, only few loci are known to have a clear role in the predisposition to this disease. Some studies reported a diagnosis of MPNs and multiple myeloma (MM) in the same patients, but the biological causes are still unclear. We tested the hypothesis that the two diseases share at least partly the same genetic risk loci. In the context of a European multicenter study with 460 cases and 880 controls, we analyzed the effect of the known MM risk loci, individually and in a polygenic risk score (PRS). The most significant result was obtained among patients with chronic myeloid leukemia (CML) for PS0RS1C1‐rs2285803, which showed to be associated with an increased risk (OR = 3.28, 95% CI 1.79‐6.02, P = .00012, P = .00276 when taking into account multiple testing). Additionally, the PRS showed an association with MPN risk when comparing the last with the first quartile of the PRS (OR = 2.39, 95% CI 1.64‐3.48, P = 5.98 × 10−6). In conclusion, our results suggest a potential common genetic background between MPN and MM, which needs to be further investigated.

Chronic neutrophilic leukemia complicated with monoclonal gammopathy of undetermined significance: A case report and literature review

“…This phenomenon suggests that CNL may be more inclined to coexist with MGUS or MM instead of coexisting by chance. The common genetic susceptibility loci in MPN and MM, and chronic inflammatory bone marrow microenvironment in MPN that in favor of the proliferation of monoclonal B cells, may be the pathogenesis of concurrence of these two different diseases 15–17 …”

“…The common genetic susceptibility loci in MPN and MM, and chronic inflammatory bone marrow microenvironment in MPN that in favor of the proliferation of monoclonal B cells, may be the pathogenesis of concurrence of these two different diseases. [15][16][17] Among the 12 cases we summarized, 11 cases detected CSF3R mutation and 7 cases were positive. We found that CSF3R was the most common mutation among the 12 cases.…”

“…The common genetic susceptibility loci in MPN and MM, and chronic inflammatory bone marrow microenvironment in MPN that in favor of the proliferation of monoclonal B cells, may be the pathogenesis of concurrence of these two different diseases. 15 , 16 , 17 …”

Germline ERBB2/HER2 Coding Variants Are Associated with Increased Risk of Myeloproliferative Neoplasms

“…It is possible, however, that germline variants induce a chronic, low-level of ERBB signaling and subsequent activation of the JAK/STAT, PI3K/AKT, or MEK/ERK pathways, with convergence on common downstream targets. Alternatively, ERBB2 may exert its predisposition to MPN acquisition by pathways that are not intrinsic or specific to hematopoietic cell signaling or development, such as genomic instability, inflammation, telomere biology, or other pathways implicated in cancer susceptibility [17,[45][46][47].…”

A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk

“…12,[21][22][23][24][25] This feature is particularly evident in MM since we observed, using GWAS Catalog, that 17 of the 24 associated polymorphisms ($71%) are pleiotropic or in high linkage disequilibrium (LD) (r 2 > 0.8) with SNPs associated with other traits (https://www. ebi.ac.uk/gwas/), including telomere length, 26 BMI 27 and risk of various cancers, such as myeloproliferative neoplasms 28 and pancreatic cancer. 25 Therefore, the aim of this study was to test the impact of all the SNPs associated at genome-wide significant level with any human trait on risk of MM.…”