Plasma Cells from Secondary Plasma Cell Leukemia Display Different Cytogenetics Pattern When Compared with Primary Plasma Cell Leukemia.
Authors: Gonzalez-Paz Natalia C. , Van Wier Scott , Santana-Davila Rafael , Ahmann Gregory , Price-Troska Tammy , Henderson Kimberly , Gertz Morie , Kyle Robert , Greipp Philip , Fonseca Rafael 
Published: April 2020

Abstract
Background: Plasma cell leukemia (PCL) is a rare plasma cell (PC) dyscrasia which may be designated as primary (PPCL) or de novo PCL when recognized at the time of diagnosis and secondary (SPCL) when there is leukemic transformation of a previously recognized multiple myeloma (MM). PCL has been reported to exhibit distinct clinical and immunophenotypic features that distinguish it from MM, but little is known about the specific genetics of this disease. To better understand the genetic features of the clonal PC from PPCL and SCPL we assessed in these patients the molecular and cytogenetic abnormalities most commonly found in MM.
Patients and Methods: In our study we analyzed 3 groups of patients; 18 with PPCL, 23 with SPCL and a control group of 345 newly diagnosed MM previously published. Diagnostic criteria for PCL followed the presence of &gt;2 x103/L PC in PB (Kyle et al. Arch Intern Med1974; 133–813–8). Cytogenetic abnormalities were assessed by the c-Ig FISH method; mutational analysis was performed using Conformational-sensitive gel electrophoresis (CSGE). Methylation was analyzed by methyl specific PCR (MSP) after bisulfite genomic DNA modification.
Results: Translocation of immunoglobulin heavy chain with Cyclin D1 (t (11; 14)) was present in 76.9% (10 of 13) of PPCL, 71% (5 of 7) of SPCL, in contrast to 15.8% (53 of 336) of MM cases. Translocations’ involving the FGFR3-MMSET genes (4p16.3 locus) and c-MAF (16q32) genes were not observed among 10 patients studied with PPCL, but were present in 12.7 % each in SPCL. The t (4;14)(p16;q32) was present in 12.7% cases of MM and the t(14;16)(q32;q23) was present in 4.6 % of MM cases. Deletion of 17p13.1 (p53 locus) was found in 10% (37 of 345) of MM cases, 53.8% (7 of 13) for PPCL and 42.8% (3 of 7) for SPCL. Deletion of 13q was present in 54.2% (176 of 325) of MM, 76.9 % (10 of 13) of PPCL and 57.1% of SPCL. Ras mutations were found in 15% (2/13) of PPCL, located in codon 1 and 2 of the K-ras gene. In addition, 23% for SPCL presented mutations in the N-ras gene. Two mutations were located in codon 2 of N-ras and 1 patients in showed a mutation in codon 1 of K-ras gene. Ras mutations were present in 27% of MM cases. Mutations for p53 gene were present in 30.7% (4/13) of PPCL, 17% (3/17) for SPCL and 5% for MM. Methylation specific PCR for p16 gene was found in 23% (3/13) of PPCL, 29% of SPCL and 33.9% (149/439) of MM. Hypermethylation of p14 was not detected in PPCL but a 23 % was found in SPCL.
Conclusions: In this study we demonstrate that PCs from PPCL more frequently carry the t (11; 14). Comparing SPCL and MM, PC’s from de novo PPCL do not show t (4; 14) or (16; 14). Deletion of 13q was more prevalent among patients with PPCL. Ras mutations appear to be as frequent in MM as in PPCL and SPCL. Mutations in p53 appeared to be more prevalent in PPCL than in SPCL and MM. Hypermethylation of p16 does not differ while hypermethylation of p14 is more frequent in SPCL than PPCL. These characteristics may lead to a different onset or disease evolution of PPCL compared to MM and secondary plasma cell leukemia and this may be important for diagnostic and treatment.