Chronic-phase chronic myeloid leukemia: Not always a reassuring diagnosis

none3noOrlandi, Ester M; Elena, Chiara; Zibellini, SilviaOrlandi, Ester M; Elena, Chiara; Zibellini, Silvi

Increased risk of lymphoid neoplasm in patients with myeloproliferative neoplasm: a study of 1,915 patients

Within a cohort of 1,915 consecutive patients with myeloproliferative neoplasm followed for a median time of 5.2 years (range 0–33.3), we investigated the occurrence of lymphoid neoplasm with the aim of defining this risk and to investigate the role of genetic predisposing factors. We identified 22 patients with myeloproliferative neoplasm who developed lymphoid neoplasm over their lifetime. We found that the risk of developing lymphoid neoplasm was 2.79-fold higher (95% CI, 1.80–4.33; P<0.001) than that of the general Italian population. A tag SNP surrogate for JAK2 GGCC haplotype was used to clarify a potential correlation between lymphoid-myeloid neoplasm occurrence and this genetic predisposing factor. As we did not find any difference in GGCC haplotype frequency between patients with both myeloid and lymphoid neoplasm and patients with myeloid neoplasm, JAK2 GGCC haplotype should not be considered a genetic predisposing factor. No difference in familial clustering was observed between the two groups

CLLU1 expression distinguishes chronic lymphocytic leukemia from other mature B-cell neoplasms

The distinction of CLL from other mature B-cell neoplasms, especially from leukemic forms of mantle cell lymphoma or splenic marginal zone lymphoma, can be difficult but has important prognostic and therapeutic implications. We measured CLLU1 (CLL upregulated gene1) mRNA by qPCR and found a highly significant difference between CLL and other lymphoid neoplasms (AUC 0.96, 95%CI 0.93-0.99). Based on our cut-off values we can predict CLL and other mature B-cell neoplasms with high probability (PPV 99% and 94%). Analysis of CLLU1 expression is a rapid and reliable tool that may facilitate the diagnosis of mature B-cell neoplasms especially in inconclusive cases

Stereotyped patterns of B-cell receptor in splenic marginal zone lymphoma

Antigen stimulation may be important for splenic marginal zone lymphoma pathogenesis. To address this hypothesis, the occurrence of stereotyped B-cell receptors was investigated in 133 SMZL (26 HCV+) compared with 4,414 HCDR3 sequences from public databases. Sixteen SMZL (12%) showed stereotyped BCR; 7 of 86 (8%) SMZL sequences retrieved from public databases also belonged to stereotyped HCDR3 subsets. Three categories of subsets were identified: i) "SMZL-specific subsets" (n=5), composed only of 12 SMZL (9 HCV-from our series); ii) "Non-Hodgkin’s lymphoma-like subsets" (n=5), comprising 5 SMZL (4 from our series) clustering with other indolent lymphomas; iii) “CLL-like subsets” (n=6), comprising 6 SMZL (3 from our series) that belonged to known CLL subsets (n=4) or clustered with public CLL sequences. Immunoglobulin 3D modeling of 3 subsets revealed similarities in antigen binding regions not limited to HCDR3. Overall, data suggest that the pathogenesis of splenic marginal zone lymphoma may involve also HCV-unrelated epitopes or an antigenic trigger common to other indolent lymphomas

Haematological malignancies in relatives of patients affected with myeloproliferative neoplasms

Abstract In a cohort of 3131 patients with myeloproliferative neoplasms (MPNs), we identified 200 patients (6.4%) who reported a second case of haematological malignancies (HM) in first‐ or second‐degree relatives. The occurrence of a second HM in the family was not influenced by MPN subtype, sex or driver mutation, while it was associated with age at MPN diagnosis: 8.5% of patients diagnosed with MPN younger than 45 years had a second relative affected with HM compared to 5.5% of those diagnosed at the age of 45 years or older (p = 0.003), thus suggesting a genetic predisposition to HM with early onset

Immunogenetics features and genomic lesions in splenic marginal zone lymphoma

Splenic marginal zone lymphomas (MZL) express mutated (M)) or unmutated (U)) immunoglobulin heavy chain (IGHV) genes. To investigate the IGHV mutational status impact on genetic lesions, this study combined single nucleotide polymorphism-arrays and IGHV sequencing in 83 cases. Clinical features and outcome were similar between U- and M-IGHV cases. Recurrent lesions frequency was higher in U-IGHV cases, including poor prognosticators. Frequencies differed among cases bearing individual IGHV genes or lambda light chains. In conclusion, SMZL comprises subgroups based on genetic abnormalities and immunogenetic status. Genomic lesion frequency differed and was higher in U-IGHV cases, possibly affecting the outcome

MYD88L265P Detection in IgM Monoclonal Gammopathies: Methodological Considerations for Routine Implementation

In IgM monoclonal gammopathies MYD88L265P is a prognostic and predictive biomarker of therapy response. MYD88L265P detection is mainly performed by allele-specific quantitative PCR (ASqPCR), however recently, droplet digital PCR (ddPCR) has been proved to be suitable for MYD88L265P screening and minimal residual disease monitoring (MRD). This study compared ASqPCR and ddPCR to define the most sensitive method for MYD88L265P detection in bone marrow (BM), peripheral blood (PB) sorted or unsorted CD19+ cells, and in plasma cell-free DNA (cfDNA). Overall, the analysis showed a good concordance rate (74%) between the two methods, especially in BM samples, while discordances (26%) were mostly in favor of ddPCR (ddPCR+ vs. ASqPCR-) and were particularly evident in samples with low mutational burden, such as PB and cfDNA. This study highlights ddPCR as a feasible approach for MYD88L265P detection across different specimen types (including cfDNA). Interestingly, its high sensitivity makes CD19+ selection dispensable. On the other hand, our results showed that MYD88L265P detection on PB samples, especially with ASqPCR, is suboptimal for screening and MRD analysis. Finally, significantly different MYD88L265P mutational levels observed between Waldenstr\uf6m Macroglobulinemia and IgM monoclonal gammopathy of undetermined significance patients suggest the need for further studies in order to identify possible correlations between mutational levels and risk of progression to Waldenstr\uf6m