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. 2017 Apr;102(4):e144-e147.
doi: 10.3324/haematol.2016.154450. Epub 2016 Dec 7.

Integration of B-cell receptor-induced ERK1/2 phosphorylation and mutations of SF3B1 gene refines prognosis in treatment-naïve chronic lymphocytic leukemia

Chiara Cavallini  1 , Carlo Visco  2 , Santosh Putta  3 , Davide Rossi  4 , Elda Mimiola  5 , Norman Purvis  6 , Ornella Lovato  1 , Omar Perbellini  2 , Erika Falisi  2 , Monica Facco  7 , Livio Trentin  7 , Maria G Romanelli  8 , Gianpietro Semenzato  7 , Achille Ambrosetti  5 , Gianluca Gaidano  9 , Giovanni Pizzolo  5 , Alessandra Cesano  10 , Maria T Scupoli  11   5
Affiliations

Integration of B-cell receptor-induced ERK1/2 phosphorylation and mutations of SF3B1 gene refines prognosis in treatment-naïve chronic lymphocytic leukemia

Chiara Cavallini et al. Haematologica. 2017 Apr.
No abstract available

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Figures

Figure 1.
Figure 1.
ERK1/2 phosphorylation in B cells from CLL patients. (A) Representative flow cytometry histograms of pERK1/2 in the basal condition or following BCR modulation with anti-IgM in CD5+/CD19+ cells from CLL patients, compared with autofluorescence signals. (B) pERK1/2 in CLL patients, in the basal condition and following anti-IgM modulation (n=152). Data are expressed as equivalent number of reference fluorophores (ERF). The results for basal and anti-IgM-modulated CLL cells were compared by the two-sample Wilcoxon signed rank sum test. The lines indicate the medians. The Y-axis is expanded on low values. (C–D) SCNP signals of pERK1/2 in the basal condition (C) and in response to anti-IgM stimulation (D) was associated with IGHV status (n=134), CD38 expression (n=152), and cytogenetic mutations (n=141). Different sample sizes depend on availability of biological parameters. Data are expressed as equivalent number of reference fluorophores (ERF) (C) and Uu (D) and represented as Tukey boxes and whiskers. The Mann-Whitney test and Kruskal-Wallis test were used for comparisons. NS: not significant.
Figure 2.
Figure 2.
Association of ERK1/2 phosphorylation in response to BCR stimulation with gene mutations. (A) ERK1/2 phosphorylation in response to anti-IgM stimulation (anti-IgM→pERK1/2) (n=152), expressed by the Uu metric, was associated with IGHV status, CD38 expression, NOTCH1, SF3B1 and TP53 mutations, and cytogenetic mutations. Rows correspond to parameters and columns represent individual patients. Data are colored in: green = high IgM→pERK1/2, red = positive for standard prognostic parameters, blue = presence of gene mutation, orange = positive for p53 dysfunction (TP53 mutation and/or del(17p)), gray = negative, white = no available data. (B) anti-IgM→pERK1/2, expressed as Uu values, was associated with SF3B1 mutation in the entire set of patients (left panel; n=146) and in the UM-CLL subset (right panel). Lines represent the mean values. Comparisons were performed using the Mann-Whitney test (left panel) and Kruskal-Wallis test (right panel).
Figure 3.
Figure 3.
Kaplan-Meier curves of time to first treatment (TTFT). Kaplan-Meier curves of TTFT for the entire patient set for which biological parameters and clinical data were available (n=125/152, A-C) or for the Binet stage A patients for whom biological parameters and clinical data were available (n=90/112, D-F). Curves were defined by pERK1/2 response to BCR (anti-IgM→pERK1/2), using the pre-specified 0.66 Uu cut-off (A,D), the presence of SF3B1 mutations (B,E), or the integrated anti-IgM→ pERK1/2 data (cut-off=0.66) and SF3B1 mutations (C,F).
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References

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