Secondary plasma cell leukaemia (PCL) with plasmablastic morphology.

A 71-year-old female with relapsed IgA lambda myeloma developed progressive cytopenia. The peripheral blood film showed 5% blastoid cells. Flow cytometry analysis was indicative of plasma cells. The bone marrow smear was packed with plasmablasts. Target CD138-cell FISH and molecular karyotyping identified a complex genome. NGS identified high-risk mutations. Bone marrow histology confirmed myeloma with no evidence of acute leukaemia. The patient was diagnosed with plasmablastic progression of myeloma and secondary PCL. Secondary PCL patients have a poor prognosis. It is essential to recognize this subtype and explore a novel treatment approach.

Clinical and cytogenetic characteristics of primary and secondary plasma cell leukemia under the new IMWG definition criteria: a retrospective study.

BACKGROUND: Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, exhibiting a more unfavorable prognosis than multiple myeloma. PCL is classified into pPCL and sPCL. Recently, the IMWG has recommended new PCL definition criteria, which require the presence of ≥5% circulating plasma cells in peripheral blood smears. Due to its low incidence, research on pPCL and sPCL is limited. METHODS: We conducted a retrospective study and analyzed clinical and cytogenetic data of pPCL and sPCL patients. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan-Meier method, and survival distributions were compared using the log-rank test. RESULTS: This is a small cohort comprising 23 pPCL and 9 sPCL patients. Notably, sPCL patients showed a higher incidence of extramedullary infiltration and a higher percentage of bone marrow plasma cells (p = 0.015 and 0.025, respectively). Although no significant difference was found between the two groups in OS and PFS, a trend emerged suggesting a superior survival outcome for pPCL patients, with a higher cumulative 1-year PFS rate (38.3% vs. 13.3%) and a lower early mortality rate (mortality rate at 3 months: 15% vs. 33%). We also suggested that pPCL patients carrying t(11;14) may have a longer median survival time than individuals with other cytogenetic abnormalities, but this was not confirmed due to the small sample size. CONCLUSION: Our study revealed clinical and cytogenetic features of pPCL and sPCL patients according to the new diagnostic criteria. The findings suggested a generally better prognosis for pPCL than sPCL and the likelihood of t(11;14) translocation acting as a favorable prognostic factor in pPCL. It is important to note that our study had a limited sample size, which may lead to bias. We hope well-designed studies can be conducted to provide more results.

Clinical and Laboratory Characteristics of IgM Primary Plasma Cell Leukemia.

BACKGROUND: The aim of the study was to investigate the clinical and laboratory characteristics of IgM primary plasma cell leukemia. METHODS: We retrospectively analyzed a case of clinical and laboratory characteristics of IgM primary plasma cell leukemia and review related literature of patient with primary plasma cell leukemia. RESULTS: Laboratory tests: Alanine aminotransferase 128 U/L, Aspartate aminotransferase 245 U/L, Globulin 47.8 g/L, Lactate dehydrogenase 1,114 U/L, Creatinine 111.7 mol/L, Serum calcium 2.47 mmol/L, ß2 microglobulin 8.52 µg/mL, Immunoglobulin G 31.41 g/L, D-dimer 2.34 mg/L, Prothrombin time 13.6 seconds Fibrinogen 2 g/L, White blood cell 7.38 x 109/L, Red blood cell 3.46 x 1012/L, Hemoglobin 115 g/L, Platelet 7 x 109/L, and 12% Primitive naive cells can be seen in peripheral blood smear. Bone marrow smear: Accounted for 52% of original cells, the cell size, shape is irregular, the edge is not neat, the cell quality is rich, stained gray blue, cytoplasmic staining uneven, some devouring blood cells can be seen in the cytoplasm or unknown substance, the nucleus shape is irregular, visible distortion and fold, is visible on the part of the nuclei cavitation sample inclusions, chromatin is meticulous, partly visible large nucleoli. Flow cytometry results showed abnormal cell group held 23.85% of nuclear cells, expression of CD38, CD138, CD117, cKappa, partly CD20, weak expressing CD45, not express CD27, CD19, CD56, CD200, CD81, cLambda. It was a monoclonal plasma cell with an abnormal phenotype, consistent with a plasma cell tumor. Immunofixation electrophoresis results showed that the serum M protein was 22.80 g/L, which was IgG-κ type, the serum free KAP light chain was 232.69 mg/L, the serum free LAM light chain was 5.37 mg/L, and the rFLC (κ-FLC: λFLC) was 43.33. The diagnosis was primary plasmacytic leukemia of light chain type. CONCLUSIONS: Primary plasma cell leukemia (pPCL) is a rare and highly aggressive plasma cell malignancy. Laboratory staff should pay more attention to and recognize the pleomorphic morphology of neoplastic plasma cells, which can enable timely clinical development of bone marrow smear, biopsy, flow cytometry, and cytogenetic tests providing help in early diagnosis and treatment.

Identification of signature genes and drug candidates for primary plasma cell leukemia: An integrated system biology approach.

BACKGROUND: Plasma cell leukemia (PCL) is one of the rare cancer which is characterized by the uncontrolled proliferation of plasma cells in peripheral blood and bone marrow. The aggressive behavior of the disease and high mortality rate among PCL patients makes it a thirst area to be explored. METHODS: The dataset for PCL was obtained from the GEO database and was analyzed using GEO2R for differentially expressed genes. Further, the functional enrichment analysis was carried out for DEGs using DAVID. The protein-protein interactions (PPI) for DEGs were obtained using STRING 11.5 and were analyzed in Cytoscape 3.7.2. to obtain the key hub genes. These key hub genes were investigated for their interaction with suitable drug candidates using DGIdb, DrugMAP, and Schrodinger's version 2022-1. RESULTS: Out of the total of 104 DEGs, 39 genes were up-regulated whereas 65 genes were down-regulated. A total of 11 biological processes, 2 cellular components, and 5 molecular functions were enriched along with the 7 KEGG pathways for the DEGs. Further, a total of 11 hub genes were obtained from the PPI of DEGs of which TP53, MAPK1, SOCS1, MBD3, and YES1 were the key hub genes. Oxaliplatin, mitoxantrone, and ponatinib were found to have the highest binding affinity towards the p53, MAPK1, and YES1 proteins respectively. CONCLUSION: TP53, MAPK1, SOCS1, MBD3, and YES1 are the signature hub genes that might be responsible for the aggressive prognosis of PCL leading to poor survival rate. However, p53, MAPK1, and YES1 can be targeted with oxaliplatin, mitoxantrone, and ponatinib.

Identification of High-Risk Multiple Myeloma With a Plasma Cell Leukemia-Like Transcriptomic Profile.

PURPOSE: Primary plasma cell leukemia (pPCL) is an aggressive subtype of multiple myeloma, which is distinguished from newly diagnosed multiple myeloma (NDMM) on the basis of the presence of ≥ 20% circulating tumor cells (CTCs). A molecular marker for pPCL is currently lacking, which could help identify NDMM patients with high-risk PCL-like disease, despite not having been recognized as such clinically. METHODS: A transcriptomic classifier for PCL-like disease was bioinformatically constructed and validated by leveraging information on baseline CTC levels, tumor burden, and tumor transcriptomics from 154 patients with NDMM included in the Cassiopeia or HO143 trials and 29 patients with pPCL from the EMN12/HO129 trial. Its prognostic value was assessed in an independent cohort of 2,139 patients with NDMM from the HOVON-65/GMMG-HD4, HOVON-87/NMSG-18, EMN02/HO95, MRC-IX, Total Therapy 2, Total Therapy 3, and MMRF CoMMpass studies. RESULTS: High CTC levels were associated with the expression of 1,700 genes, independent of tumor burden (false discovery rate < 0.05). Of these, 54 genes were selected by leave-one-out cross-validation to construct a transcriptomic classifier representing PCL-like disease. This not only demonstrated a sensitivity of 93% to identify pPCL in the validation cohort but also classified 10% of NDMM tumors as PCL-like. PCL-like MM transcriptionally and cytogenetically resembled pPCL, but presented with significantly lower CTC levels and tumor burden. Multivariate analyses in NDMM confirmed the significant prognostic value of PCL-like status in the context of Revised International Staging System stage, age, and treatment, regarding both progression-free (hazard ratio, 1.64; 95% CI, 1.30 to 2.07) and overall survival (hazard ratio, 1.89; 95% CI, 1.42 to 2.50). CONCLUSION: pPCL was identified on the basis of a specific tumor transcriptome, which was also present in patients with high-risk NDMM, despite not being clinically leukemic. Incorporating PCL-like status into current risk models in NDMM may improve prognostic accuracy.

Immunoglobulin heavy chain gene rearrangement in heavy chain deposition disease suggests it is a plasma cell disease: a case report.

Heavy chain deposition disease (HCDD) is characterized by the deposition of truncated monoclonal immunoglobulin heavy chains along glomerular basement membranes. Truncated heavy chains are thought to be associated with plasma cell disease (PCD), but previous bone marrow cytology tests showed that only 30% of HCDD cases are related to PCDs. We report the first known use of immunoglobulin heavy chain (IGH) gene rearrangement to diagnose a patient with γ3-HCDD, although bone marrow morphology test identified no abnormalities. Our findings provide strong evidence for a correlation between PCDs and HCDD, which could help understand the genetic background underlying abnormal heavy chains and assess disease prognosis. Further, concordant with previous findings, bortezomib-based chemotherapy had a good therapeutic effect in our patient. We summarize the experience of diagnosing and treating a case of HCDD, and combine this with a literature review to further explore the correlation between PCDs and HCDD, which has important clinical value.

Genetic profile of primary plasma cell leukemia in Korea: comparison with plasma cell myeloma.

Plasma cell leukemia (PCL) is clinically and genetically distinct from multiple myeloma (MM), despite controversies regarding the disease definition. To determine the distinct features of PCL, the genetic property of primary PCL (pPCL) was compared with that of secondary PCL (sPCL) and MM. In patients with pPCL, Eighty-nine non-synonymous mutations were observed in 68 genes. The most frequently mutated genes were TP53, TSC2, and TYK2. In comparison with genetic abnormalities of sPCL and MM, 45 genes were present only in pPCL while 28 genes were only in sPCL and 22 genes only in MM. Among the common genes between pPCL and MM, a higher prevalence of TP53 was observed in pPCL, compared to MM (p < 0.05), while similar, compared to sPCL (p = 0.64). In summary, pPCL patients showed a higher level of genetic heterogeneity and distinctive genetic signature in their mutational profile compared to patients with MM and sPCL.

Downregulation of ITGA6 confers to the invasion of multiple myeloma and promotes progression to plasma cell leukaemia.

BACKGROUND: Secondary plasma cell leukaemia (sPCL) is an aggressive form of multiple myeloma (MM), but the mechanism underlying MM progresses into PCL remains unknown. METHODS: Gene expression profiling of MM patients and PCL patients was analysed to identify the molecular differences between the two diseases. Cox survival regression and Kaplan-Meier analysis were performed to illustrate the impact of integrin subunit alpha 6 (ITGA6) on prognosis of MM. Invasion assays were performed to assess whether ITGA6 regulated the progression of MM to PCL. RESULTS: Gene expression profiling analyses showed that cell metastasis pathways were enriched in PCL and ITGA6 was differentially expressed between PCL and MM. ITGA6 expression was an independent prognostic factor for event-free survival (EFS) and overall survival (OS) of MM patients. Moreover, the stratification ability of the International Staging System (ISS) of MM was improved when including ITGA6 expression. Functional studies uncovered that increased ITGA6 reduced the myeloma cell invasion. Additionally, low expression of ITGA6 resulted from epigenetic downregulating of its anti-sense non-coding RNA, ITGA6-AS1. CONCLUSION: Our data reveal that ITGA6 gradually decreases during plasma cell dyscrasias progression and low expression of ITGA6 contributes to myeloma metastasis. Moreover, ITGA6 abundance might help develop MM prognostic stratification.

A longitudinal analysis of chromosomal abnormalities in disease progression from MGUS/SMM to newly diagnosed and relapsed multiple myeloma.

We analyzed variations in terms of chromosomal abnormalities (CA) by fluorescence in situ hybridization (FISH) analysis on purified bone marrow plasma cells throughout the progression from monoclonal gammopathy of undetermined significance/smoldering multiple myeloma (MGUS/SMM) to newly diagnosed MM/plasma cell leukemia (NDMM/PCL) at diagnosis and from diagnostic samples to progressive disease. High risk was defined by the presence of at least del(17p), t(4;14), and/or t(14;16). 1p/1q detection (in the standard FISH panel from 2012 onward) was not available for all patients. We analyzed 139 MM/PCL diagnostic samples from 144 patients, with a median follow-up of 71 months: high-risk CA at diagnosis (MGUS/SMM or NDMM) was present in 28% of samples, whereas 37-39% showed high-risk CA at relapse. In 115 patients with NDMM who evolved to relapsed/refractory MM, we identified 3 different populations: (1) 31/115 patients (27%) with gain of new CA (del13, del17p, t(4;14), t(14;16) or 1q CA when available); (2) 10/115 (9%) patients with loss of a previously identified CA; and (3) 74 patients with no changes. The CA gain group showed a median overall survival of 66 months vs. 84 months in the third group (HR 0.56, 95% CI 0.34-0.92, p = 0.023). Clonal evolution occurs as disease progresses after different chemotherapy lines. Patients who acquired high-risk CA had the poorest prognosis. Our findings highlight the importance of performing FISH analysis both at diagnosis and at relapse.

Plasma cell leukaemia with t(11;14) not responsive to venetoclax.

A 70-year-old man with medical history of IgG kappa multiple myeloma, initially diagnosed in 2017, underwent induction therapy with carfilzomib, lenalidomide and dexamethasone followed by autologous haematopoietic stem cell transplantation. Nine months following transplant, disease relapsed in the form of plasma cell leukaemia. Fluorescent in situ hybridisation of malignant plasma cells revealed t(11;14). A combination therapy including venetoclax was used based on efficacy data for Bcl-2 inhibitor venetoclax from available early-phase clinical trials in patients with relapsed multiple myeloma with t(11;14) and other published case studies. Unfortunately, the disease was primary refractory, and after further ineffective therapies, the patient did not have a successful outcome.

Single-Cell Transcriptomic Analysis Reveals BCMA CAR-T Cell Dynamics in a Patient with Refractory Primary Plasma Cell Leukemia.

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the clinical treatment of hematological malignancies due to the prominent anti-tumor effects. B cell maturation antigen (BCMA) CAR-T cells have demonstrated promising effects in patients with relapsed/refractory multiple myeloma. However, the dynamics of CAR-T cell proliferation and cytotoxicity in clinical patients remains unexplored. Here, we longitudinally profiled the transcriptomes of 55,488 T cells including CAR-T products, CAR-T cells, and endogenous T cells at the peak and remission phases in a plasma cell leukemia (PCL) patient treated with BCMA CAR-T cells by single-cell transcriptomic analysis. Our results showed distinct CAR-T and endogenous T cell subsets indicating stage-specific expression in proliferation, cytotoxicity, and intercellular signaling pathways. Furthermore, we found that CAR-T cells at peak phase gradually convert to a highly cytotoxic state from a highly proliferative state along a development trajectory. Moreover, re-analysis of a single cell study from CD8+ CD19 CAR-T confirmed our findings. These commonalities suggest conserved mechanisms for CAR-T treatment across hematological malignancies. Taken together, our current study provides insight into CAR-T cell dynamics during CAR-T therapy and proves that both BCMA CAR-T and CD19 CAR-T have similar transcriptional characteristics, especially at the CAR-T peak phase.

Dickkopf-related protein 1 expression in bone marrow of multiple myeloma patients: correlation with bone disease and plasma cell malignancy type.

BACKGROUND: Previous studies have pointed out the role of dickkopf-related protein 1 (DKK 1) - Wnt inhibitor, which is essential for osteoblast functioning, in the development of osteolytic lesions in multiple myeloma (MM). AIM: To assess the DKK 1 expression displayed by myeloma cells in bone marrow trephine biopsies of patients with and without osteolytic lesions, and in different malignancy grades of the disease. METHODS: The expression level of DKK 1 was assessed immunohistochemically in bone marrow of 49 MM patients presented with and without osteolytic lesions (the 1st and the 2nd group, respectively). RESULTS: Levels of weak, moderate, and strong DKK 1 expression were distributed - as 43.33, 27.78 and 25.56%, and 63.91, 18.80, and 1.50%, respectively when evaluating the samples obtained from the 1st and the 2nd group. Statistically significant differences were found when the levels of DKK 1 expression in the 1st and the 2nd group were compared (χ2 = 51; df = 3; p < 0.001). CONCLUSIONS: DKK 1 contributes to the development of osteolytic lesions in MM. The present study provides morphological evidence that inhibition in Wnt signaling may lead to bone damage observed in the advanced stage of the disease.

[Prognosis and Genetic Characteristics of Patients with Plasma Cell Leukemia].

OBJECTIVE: To evaluate the clinical characteristics, genetic abnormalities, treatment efficacy and prognostic factors in patients with plasma cell leukemia(PCL). METHODS: 30 patients diagnosed as PCL in our hospital from January 1993 to December 2019 were enrolled, and the clinical characteristics, laboratory findings, therapeutic regimes, and survival data of the patients were retrospectively analyzed. RESULTS: The median age of the 30 patients was 56.5 (28-80) years old, among them, 25 patients were primary plasma cell leukemia, and 5 patients were secondary plasma cell leukemia. Complex karyotypes and subdiploids were most common in cytogenetic abnormalities. Among the 20 cases of chromosome G banding, 11 (55%) cases were complex karyotypes and 8 (40%) cases were hypodiploid. Fluorescent in situ hybridization (FISH) test showed that among 11 cases, 6 cases showed 17p13 deletion, 8 cases showed at least two kinds of abnormalities, which including t (14; 16), t (8; 14), t (11;14), 17p13 deletion, and 13q14 deletion. The median overall survival (OS) time was 10.5 months for all patients. The median OS time of the patients in ECOG score ≤ 2 group was 21.5 months, which was significantly longer than those in the ECOG score>2 group(1.2 months) (P=0.017). The median OS time of the patients treated with novel agents (including proteasome inhibitor and/or immunomodulator) was 24.9 months, which was significantly longer than the patients treated with traditional chemotherapy group(10.5 months) (P＜0.001). For the patients treated with novel agents, the median OS time of patients accepted two novel agents combination was 30.9 months, which was longer than those of single novel agent(11.5 months) (P=0.021). The effect of genetic abnormolity to the OS of the patients showed no statistical difference. Multivariate statistical analysis showed that ECOG score>2 was the independent prognostic factor of plasma cell leukemia patients. There were two patients underwent allogeneic hematopoietic stem cell transplantation in the study,but died due to the pulmonary infection within 6 months after transplantation. CONCLUSION: In the era of novel agents, ECOG score is an independent prognostic factor of plasma cell leukemia. Multiple novel agents treatment should be underwent as soon as possible to improve the prognosis of the patients. Pulmonary infection is a common factor that cause the death of the patients after allogeneic hematopoietic stem cell transplantation.

Genomic analysis of primary plasma cell leukemia reveals complex structural alterations and high-risk mutational patterns.

Primary plasma cell leukemia (pPCL) is a rare and aggressive form of multiple myeloma (MM) that is characterized by the presence of ≥20% circulating plasma cells. Overall survival remains poor despite advances of anti-MM therapy. The disease biology as well as molecular mechanisms that distinguish pPCL from non-pPCL MM remain poorly understood and, given the rarity of the disease, are challenging to study. In an attempt to identify key biological mechanisms that result in the aggressive pPCL phenotype, we performed whole-exome sequencing and gene expression analysis in 23 and 41 patients with newly diagnosed pPCL, respectively. The results reveal an enrichment of complex structural changes and high-risk mutational patterns in pPCL that explain, at least in part, the aggressive nature of the disease. In particular, pPCL patients with traditional low-risk features such as translocation t(11;14) or hyperdiploidy accumulated adverse risk genetic events that could account for the poor outcome in this group. Furthermore, gene expression profiling showed upregulation of adverse risk modifiers in pPCL compared to non-pPCL MM, while adhesion molecules and extracellular matrix proteins became increasingly downregulated. In conclusion, this is one of the largest studies to dissect pPCL on a genomic and molecular level.

MYC amplification on double minute chromosomes in plasma cell leukemia with double IGH/CCND1 fusion genes.

In multiple myeloma (MM), MYC rearrangements that result in increased MYC expression are associated with an aggressive form of MM and adverse outcome. However, the consequences of MYC amplification in MM remain unclear. Here, we describe an unusual case of plasma cell leukemia (PCL) harboring MYC amplification on double minute chromosomes (dmin). A 79-year-old woman was initially diagnosed as having BJP-κ type MM with bone lesions. After seven months, the disease progressed to secondary PCL: leukocytes 49.1 × 109/L with 77% plasma cells showing lymphoplasmacytic appearance. The bone marrow was infiltrated with 76% plasma cells immunophenotypically positive for CD38 and negative for CD45, CD19, CD20, and CD56. The karyotype by G-banding and spectral karyotyping was 48,XX,der(14)t(11;14)(q13;q32),+der(14)t(14;19)(q32;q13.1),+18,6~95dmin[15]/46,XX[5]. Fluorescence in situ hybridization detected multiple MYC signals on dmin and double IGH/CCND1 fusion signals on der(14)t(11;14) and der(14)t(14;19). Most plasma cells were diffusely and strongly positive for MYC and CCND1 by immunohistochemistry. The patient died of progressive disease after one week. MYC amplification led to high expression of MYC and rapid disease progression, indicating its clinical significance in the pathogenesis of MM/PCL. MYC amplification on dmin may be a very rare genetic event closely associated with the progression to PCL and coexistence of IGH/CCND1 fusions.

Prognosis and Genetic Characteristics of Patients with Plasma Cell Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the clinical characteristics, genetic abnormalities, treatment efficacy and prognostic factors in patients with plasma cell leukemia(PCL).@*METHODS@#30 patients diagnosed as PCL in our hospital from January 1993 to December 2019 were enrolled, and the clinical characteristics, laboratory findings, therapeutic regimes, and survival data of the patients were retrospectively analyzed.@*RESULTS@#The median age of the 30 patients was 56.5 (28-80) years old, among them, 25 patients were primary plasma cell leukemia, and 5 patients were secondary plasma cell leukemia. Complex karyotypes and subdiploids were most common in cytogenetic abnormalities. Among the 20 cases of chromosome G banding, 11 (55%) cases were complex karyotypes and 8 (40%) cases were hypodiploid. Fluorescent in situ hybridization (FISH) test showed that among 11 cases, 6 cases showed 17p13 deletion, 8 cases showed at least two kinds of abnormalities, which including t (14; 16), t (8; 14), t (11;14), 17p13 deletion, and 13q14 deletion. The median overall survival (OS) time was 10.5 months for all patients. The median OS time of the patients in ECOG score ≤ 2 group was 21.5 months, which was significantly longer than those in the ECOG score>2 group(1.2 months) (P=0.017). The median OS time of the patients treated with novel agents (including proteasome inhibitor and/or immunomodulator) was 24.9 months, which was significantly longer than the patients treated with traditional chemotherapy group(10.5 months) (P＜0.001). For the patients treated with novel agents, the median OS time of patients accepted two novel agents combination was 30.9 months, which was longer than those of single novel agent(11.5 months) (P=0.021). The effect of genetic abnormolity to the OS of the patients showed no statistical difference. Multivariate statistical analysis showed that ECOG score>2 was the independent prognostic factor of plasma cell leukemia patients. There were two patients underwent allogeneic hematopoietic stem cell transplantation in the study,but died due to the pulmonary infection within 6 months after transplantation.@*CONCLUSION@#In the era of novel agents, ECOG score is an independent prognostic factor of plasma cell leukemia. Multiple novel agents treatment should be underwent as soon as possible to improve the prognosis of the patients. Pulmonary infection is a common factor that cause the death of the patients after allogeneic hematopoietic stem cell transplantation.

Transcriptome analysis reveals significant differences between primary plasma cell leukemia and multiple myeloma even when sharing a similar genetic background.

Primary plasma cell leukemia (pPCL) is a highly aggressive plasma cell dyscrasia characterised by short remissions and very poor survival. Although the 17p deletion is associated with poor outcome and extramedullary disease in MM, its presence does not confer the degree of aggressiveness observed in pPCL. The comprehensive exploration of isoform expression and RNA splicing events may provide novel information about biological differences between the two diseases. Transcriptomic studies were carried out in nine newly diagnosed pPCL and ten MM samples, all of which harbored the 17p deletion. Unsupervised cluster analysis clearly distinguished pPCL from MM samples. In total 3584 genes and 20033 isoforms were found to be deregulated between pPCL and MM. There were 2727 significantly deregulated isoforms of non-differentially expressed genes. Strangely enough, significant differences were observed in the expression of spliceosomal machinery components between pPCL and MM, in respect of the gene, isoform and the alternative splicing events expression. In summary, transcriptome analysis revealed significant differences in the relative abundance of isoforms between pPCL and MM, even when they both had the 17p deletion. The mRNA processing pathway including RNA splicing machinery emerged as one of the most remarkable mechanisms underlying the biological differences between the two entities.