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Letters to the Editor
Table 2. Characteristics of patients with myeloproliferative neoplasms and CCND2 mutations.
Patient Age Sex Diagnosis
#1 41 F ET
#2 48 M PV
Driver mutation
CALR type 1 JAK2 p.V617F
CCND2 VAF mutation
c.839C>T p.T280I 2,4%
c.838A>G p.T280A 1%
Other Time mutations from
(VAF) diagnosis to NGS (months)
None 107
None 37
Treatments received
None
Interferon a
#3 41 F ET
#4 75 M MF
JAK2 p.V617F MPL p.W515L
c.812C>A p.Ser271*
c.842C>G p.P281R
1%
2,4% to
5,1%
CBL p.C381Y (5%) 69 NRAS p.G12V (6%)
CBL p.Y371* (11%) 25
IDH1 p.R132H (37%)
SRSF2 p.P95L (39%) TET2 p.P739Lfs*12 (6%)
Ruxolitinib
Ruxolitinib
MPN: myeloproliferative neoplasms; ET: essential thrombocythemia; PV: polycythemia vera; MF: myelofibrosis; M: male; f: female;VAF: variant allelic frequencies; NGS: next- generation sequencing.
disease before the occurrence of transformation to MF or leukemia has been clearly demonstrated, making it essen- tial to precisely define the clonal architecture of patients. Although rare (less than 1% of our cohort) the CCND2 mutations may participate in the disease evolution in some patients. Indeed, as D-type cyclins such as D1, D2 and D3 cyclins are essential partners for cyclin-depen- dent kinases (mostly CDK4 and CDK6), the mutations targeting CCND2 described in this study are likely to induce a deregulation of the cell cycle and may partici- pate in the development of more aggressive clones. This deserves further studies to assess the specific role of these rare mutations.
Bruno Cassinat,1,2,3 Emmanuelle Verger,1,2 Nabih Maslah,1,2 Nicolas Gauthier,4 William Vainchenker,3,5
Stéphane Giraudier1,2,3 and Jean-Jacques Kiladjian2,3,4
1AP-HP, Laboratoire de Biologie Cellulaire, Hôpital Saint-Louis, Paris; 2Université de Paris, U1131 INSERM, Paris; 3Laboratoire d’Excellence GR-Ex, Université de Paris, Paris; 4Centre d’Investigations Cliniques, Hôpital Saint-Louis, Paris and 5Université de Paris-Saclay, INSERM UMR1287, Institut Gustave Roussy, Villejuif, France
Correspondence: JEAN-JACQUES KILADJIAN - jean-jacques.kiladjian@aphp.fr
doi:10.3324/haematol.2020.252643
Disclosures: no conflicts of interest to disclose.
Contributions: EV, NM and NG performed the research and ana- lyzed the data; SG and WV recruited patients and contributed essen-
tial clinical data; BC and JJK designed the research, analyzed results and wrote the paper.
Acknowledgments: the authors would like to thank the staff of the Laboratoire de Biologie Cellulaire for excellent technical help and the French Intergroup for Myeloproliferative neoplasms (FIM) for thoughtful discussions.
References
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