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. 2016 Apr;101(4):e135-8.
doi: 10.3324/haematol.2015.136051. Epub 2016 Jan 27.

Clinical impact of small subclones harboring NOTCH1, SF3B1 or BIRC3 mutations in chronic lymphocytic leukemia

Silvia Rasi  1 , Hossein Khiabanian  2 , Carmela Ciardullo  1 , Lodovico Terzi-di-Bergamo  1 , Sara Monti  1 , Valeria Spina  1 , Alessio Bruscaggin  1 , Michaela Cerri  1 , Clara Deambrogi  1 , Lavinia Martuscelli  1 , Alessandra Biasi  1 , Elisa Spaccarotella  1 , Lorenzo De Paoli  1 , Valter Gattei  3 , Robin Foà  4 , Raul Rabadan  2 , Gianluca Gaidano  1 , Davide Rossi  5
Affiliations

Clinical impact of small subclones harboring NOTCH1, SF3B1 or BIRC3 mutations in chronic lymphocytic leukemia

Silvia Rasi et al. Haematologica. 2016 Apr.
No abstract available

Keywords: BIRC3; NOTCH1; SF3B1; TP53; chronic lymphocytic leukemia; evolution; frequency; prognostic impact; subclones.

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Figures

Figure 1.
Figure 1.
Molecular profile of subclonal NOTCH1, SF3B1, and BIRC3 mutations. Allele frequency of NOTCH1 (A), SF3B1 (B), and BIRC3 (C) mutations identified by ultra-deep-next generation sequencing. Mutations are ordered according to their allelic abundance. Mutations that tested positive (gray bars) and negative (red bars) by Sanger sequencing are indicated. Schematic diagram of the NOTCH1 (D), SF3B1 (E), and BIRC3 (F) proteins with their conserved functional domains. Color-coded shapes indicate the position of small subclonal mutations from the CLL study cohort (red shapes) and mutations detectable by Sanger sequencing in CLL from our internal dataset (gray shapes). Hot spot codons recurrently affected by both subclonal and clonal mutations are highlighted.
Figure 2.
Figure 2.
Estimates of overall survival (OS) of patients harboring small mutated subclones. Comparison of OS from chronic lymphocytic leukemia (CLL) diagnosis between patients harboring small subclonal mutations not detectable by Sanger sequencing (yellow line), cases harboring Sanger sequencing positive mutations (red line), and cases harboring an unmutated gene (blue line) of the NOTCH1 (A), SF3B1 (B), and BIRC3 (C) genes. P: P values by log rank test; M: mutation.
Figure 3.
Figure 3.
Longitudinal analysis of patients harboring small mutated subclones. Changes of the allele frequency of the NOTCH1 (A), SF3B1 (B), and BIRC3 (C) mutated subclones upon “watch and wait”. The upper line graph represents the allele frequency modification of each individual mutation. The lower box plot graph shows in aggregate the mean, interquartile, and extreme values of the allele frequency at diagnosis and last follow up. P values by Wilcoxon rank test. Changes of the allele frequency of the NOTCH1 (D), SF3B1 (E), and BIRC3 (F) mutated subclones upon treatment. The upper line graph represents the allele frequency modification of each individual mutation after each individual treatment. The lower box plot graph shows in aggregate the mean, interquartile, and extreme values of the allele frequency before treatment and at relapse. P: P values by Wilcoxon rank test.
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References

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