Non-Secretory Multiple Myeloma (NSMM) is characterized by typical morphological and pathological multiple myeloma (MM) characteristics and the absence of an M-protein on immunofixation electrophoresis with estimated prevalence of 3%. Among the NSMM cases there is a subset in which no cytoplasmic Immunoglobulin synthesis is detected, and this entity is called ‘’Non-Producing’’ Multiple Myeloma (NPMM). Plasma cell leukemia (PCL) is an aggressive form of MM characterized by high levels of abnormal plasma cells circulating in the peripheral blood. We present a rare case of non-producing variant of PCL. 75-year-old male was admitted due to anemia and thrombocytopenia. His CBC revealed hemoglobin of 9.0 g/dl and platelets were 9 k/ul. CMP showed creatinine of 1.34 mg/dl, total protein of 6 g/dl, albumin 3.6 g/dl and corrected calcium was normal. LDH was 204 IU/L. Peripheral smear review showed 8% circulating atypical plasmacytoid cells, normochromic normocytic anemia and thrombocytopenia. SPEP showed no monoclonal protein. IgA was normal. IgG, IgM were low 315 mg/dl and 20 mg/dl respectively. Serum beta-2 microglobulin was high (5.5, 1.1 – 2.4 mg/dl). Serum free kappa light chain was low (0.15, 0.33-1.94 mg/dl), lambda light chain and ratio was normal. Skeletal survey showed possible lytic lesions in right femur neck and subtrochanteric left femur. Bone marrow biopsy showed plasma cell myeloma involving 90-95% of bone marrow cellularity. The plasma cells show morphologic heterogeneity with prominent immature, plasmablastic and pleomorphic morphology. Flow cytometry shows a dominant abnormal CD45-dim population with expression of CD38, CD138, CD56 and CD117 (partial). The abnormal cells are negative for cytoplasmic kappa and lambda immunoglobulin light chains and negative for myeloid and lymphoid markers (by flow cytometry and immunohistochemical stains). Complex chromosomal analysis. Plasma cell FISH studies was positive for t(11;14). Based on suggested revised diagnostic criteria for PCL from outcomes of patients at mayo clinic, our patient was diagnosed with plasma cell leukemia. Given aggressive biology of this disease, he was started on VD-PACE chemotherapy. Bone marrow biopsy after cycle 1 chemotherapy showed no morphologic, immunophenotypic or flow cytometric features of a plasma cell neoplasm. Given excellent treatment response and discussion with transplant center subsequent cycle 2 was changed to Velcade, Revlimid and low-dose dexamethasone. He is scheduled for stem cell transplant later this month. Primary plasma cell leukemia (pPCL) is the most aggressive form of the plasma cell dyscrasias. The outcome of pPCL has improved with the introduction of autologous stem cell transplantation and combination approaches with novel agents, including bortezomib and immunomodulatory drugs, such as lenalidomide. This case highlights the challenges in diagnosis of non-producer primary plasma cell leukemia.

Multiple myeloma and its aggressive variant, plasma cell leukemia, are still considered to be incurable diseases despite the progressive treatment approaches comprising novel drugs. This can be attributed to the presence of the bone marrow microenvironment which plays an important role in drug resistance of myeloma cells. Hematopoietic cell lines derived from hematologic malignancies are suitable models for the study of etiopathogenesis of these malignant diseases and for testing new potential drugs. Establishment of these cell lines is still considered to be coincidental and rare event. The first part of the thesis is focused on establishment and characterization of the cell line UHKT-944 derived from a patient with primary plasma cell leukemia, and on completion of characterization of the cell line UHKT-893 derived from a patient with multiple myeloma. Additional analysis of UHKT-893 cell line were performed including sequence analysis of IgVH gene rearrangements and cytogenetic analysis which contributed to more detailed characterization of this cell line. During cultivation of UHKT-944 cells, we monitored the cell growth and confirmed dependence on interleukin-6 (IL-6). Immunophenotype analysis revealed the presence of surface markers characteristic of malignant plasma cells. UHKT-944 cells...