Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe an unusual case of small lymphocytic lymphoma with multiple prominent pseudofollicular proliferation centers in which immunohistochemistry reveals that the small cells are surface IgM kappa positive and the large pseudofollicular cells are surface IgA kappa positive. We further show by genomic DNA analysis that the tumor tissue contains two JH rearrangements, one Cmu rearrangement, one C alpha rearrangement, and a single C kappa rearrangement, strongly suggesting that the large cells within the proliferation centers have arisen from the small cells via a clonal heavy chain immunoglobulin isotype switch. Isotype switching in human lymphoma and leukemia appears to be an uncommon event. However, there are reports that strongly support isotype switching in pre-B-cell leukemia, Richter's syndrome, lymphoid blast crisis of chronic myelogenous leukemia, and multiple myeloma. To our knowledge, there have been no previous reports demonstrating isotype switching within the proliferation centers of small lymphocytic lymphoma. We present evidence of in vivo intratumoral isotype switching within the proliferation centers of a small lymphocytic lymphoma documented at the level of immunohistochemistry and DNA rearrangement.
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PMID:Clonal heavy chain isotype switching within the proliferation centers of a small lymphocytic lymphoma: implications regarding the origin of proliferation centers. 831 58

The A-myb gene encodes a transcription factor that is related both functionally and structurally to the v-myb oncogene. Following our observations that A-myb is expressed in a restricted subset of normal mature human B lymphocytes, with the phenotype CD38+, CD39-, slgM-, we have now investigated the pattern of A-myb expression in neoplastic B cells representating the whole spectrum of B-cell differentiation and compared it to that of c-myb and B-myb. In a panel of 32 B-cell lines, A-myb was very strongly expressed in most Burkitt's lymphoma (BL) cell lines, but weak or negative in 2 pre-B acute lymphoblastic leukemia (ALL), 4 non-Hodgkin's lymphoma (NHL), 6 Epstein-Barr virus-immortalized lymphoblastoid cell lines, and 6 myeloma lines. Protein expression paralleled that of the RNA. We have also investigated A-myb expression in 49 fresh cases of B leukemias. Among 24 ALL, 6 were of the null and 11 of the common type and all these were negative for A-myb expression; on the other hand, all 7 B-ALL cases (slg+), as well as one fresh BL case with bone marrow infiltration, expressed A-myb. A-myb was undetectable in 4 prolymphocytic leukemias (PLL) but was strongly expressed in 5/20 (25%) of chronic lymphocytic leukemia (CLL) samples. In the latter A-myb did not correlate with phenotype or clinical stage. Finally, we have studied the progression of one case of CLL into Richter's syndrome and have found that the Richter's cells expressed about 25-fold less A-myb RNA than the CLL cells from the same patient. The pattern of c-myb and B-myb was clearly distinct from that of A-myb. C-myb and B-myb were expressed in all neoplastic groups, except in CLL cells. Thus, A-myb expression, unlike that of c-myb and B-myb, is restricted to a subset of B-cell neoplasias (in particular BL and slg+B-ALL) representative of a specific stage of B-cell differentiation. This expression may in part reflect expression of A-myb by the normal germinal center B cells that are the normal counterpart of these transformed B cells. The data presented strongly support a role for this transcription factor in B-cell differentiation and perhaps in B-cell transformation in some neoplasias.
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PMID:Expression of A-myb, but not c-myb and B-myb, is restricted to Burkitt's lymphoma, sIg+ B-acute lymphoblastic leukemia, and a subset of chronic lymphocytic leukemias. 863 38

Non-Hodgkin's lymphomas (NHL), Hodgkin's Disease (HD), and multiple myeloma (MM) develop as second malignancies in approximately 3%, 0.5%, and 0.1%, respectively, of chronic lymphocytic leukemia (CLL) patients. The true incidence may be higher, as postmortem examination is not performed in most patients, thus underestimating occult disease. As originally described, the term Richter's syndrome (RS) refers to the development of aggressive NHL during the course of CLL. The onset of RS is usually abrupt with clinical deterioration as manifested by worsening systemic symptoms, rapid tumor growth, and/or extranodal involvement. Diagnosis requires tissue biopsy. The NHL is usually diffuse large cell (LCL) or its immunoblastic variant. It is resistant to current therapies, and the median survival of patients who develop RS is approximately 6 months. The precise relationship between the cells of origin of CLL and LCL in RS patients is unknown with data suggesting either common (60%) or distinct (40%) clonal evolutions for these malignancies in different patients. Gene rearrangement studies and isotype analysis suggest that CLL and LCL in RS patients frequently share identical clonal origins. Purine analog therapy of CLL patients does not seem to affect the incidence or clinical behavior of RS. Despite increasing rates of achievement of complete remission in CLL associated with fludarabine-based regimens, RS still occurs, warranting continued surveillance of all CLL patients regardless of disease status. HD and MM in CLL patients are usually advanced at the time of presentation and have poor response and survival rates.
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PMID:Chronic lymphocytic leukemia in (Richter's) transformation. 948 33

A fifty-nine year old woman is admitted with severe hypercalcemia and other metabolic disorders. The buffy coat showed plasmoblasts in association with chronic lymphocytic leukemia cells (CLL). Immunophenotyping revealed different light chains on CLL cells and in plasmoblasts. We discuss the association of hypercalcemia and CLL, its physiopathology and the distinction with Richter's Syndrome. We also review literature descriptions of the uncommon association of CLL and Multiple Myeloma and raise the question of its clonal origin.
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PMID:Hypercalcemia, chronic lymphocytic leukemia and multiple myeloma: uncommon association. 1054 13

Second malignancies are frequent complications in patients with chronic lymphocytic leukemia (CLL). Patients with this leukemia may develop large cell lymphoma (LCL) known as Richter's syndrome (RS). RS occurs in CLL patients of about 3% and may develop in a single lymph node or more often in a group of nodes. However, in some patients extranodal localization of aggressive lymphoma in RS has been observed. Besides LCL, Hodgkin's disease, prolymphocytoid leukemia, multiple myeloma and acute lymphoblastic leukemia may also occur as RS variants. The origin of lymphoid cells in RS remains tentative. However, CLL and RS originate from the same clone for some patients, whereas, in other patients cells of aggressive lymphoma do not have the features of the same clone as the CLL cells. The prognosis of RS is poor. Survival in different studies will be usually 2-5 months. The secondary development or coexistence of myeloproliferative disorders or myelodysplastic syndrome and solid tumors have also been rarely documented in CLL patients. It is of great concern that therapy may further increase the risk of a second neoplasm. However, until now, there are no clear evidence that alkylating agents or purine nucleoside analogs may be associated with an increased incidence of second malignancies in patients with CLL. In this review, epidemiology, biology, clinical characteristic and treatment approaches in RS and other secondary neoplasms in patients with CLL are discussed.
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PMID:Second malignancies and Richter's syndrome in patients with chronic lymphocytic leukemia. 1576 79

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia worldwide. It is an indolent disease, almost exclusively of B-cell origin. Some CLLs evolve into a more aggressive lymphoid malignancy. The most common of these is Richter's syndrome. Transformation to acute lymphoblastic leukemia, plasma cell leukemia, multiple myeloma, or Hodgkin's disease (HD) may also occur. CLL patients are also at a significantly increased risk of developing a second malignant neoplasm later in life. One of the most common of these is HD. Herein, we report a case of HD in an elderly man with a history of B-cell CLL.
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PMID:Hodgkin's disease in an elderly patient with B-cell chronic lymphocytic leukemia. 1627 18

Chronic lymphocytic leukemia/small lymphocitic lymphoma (CLL/SLL) is low-grade malignant lymphoprolipheration, that has tendency to convert to a higher-grade neoplasm over time. More common is the development of a diffuse large cell lymphoma or transformation into prolymphocytic cell population. In rare cases, 0.1-0.5% of patients develop multiple myeloma or Hodgkin's disease. We present 65-year-old female with Hodgkin's variant of Richter's syndrome. On the basis of clinical simptoms, cytological, hystological and immunohistological finding in April 2008 CLL/SLL were diagnosed. The patient was treated with 8 courses of R-CHOP. After 10 months, FNA of the one of the enlarged lymph node on the neck was performed. The diagnosis was Hodgkin's disease. Immuno-hystological studies of the lymph node was consistent with type I Hodgkin's type of Richter's syndrome. Patient was treated with 3 courses of ABVD and radiotherapy.
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PMID:Hodgkin's lymphoma variant of Richter's syndrome. 2043 46

The aim of this study is to investigate long-term outcome of symptomatic type 1 cryoglobulinemia (CG) and its determinants. Retrospective cohort study was conducted in two French University Hospitals. Patients with type 1 CG were identified using laboratory databases. Inclusion criterion was the presence of persistent symptoms of CG. Among 227 screened patients, 36 were included. Skin or vasomotor symptoms were the most frequent features (75%). Nephropathy and neuropathy occurred in 30% and 47% of cases, respectively. The underlying B cell disease (BCD) was a nonmalignant monoclonal gammopathy (NMMG) in 13 (36%) and a hematologic malignancy (HM) in 23 (64%; Waldenstrom macroglobulinemia (WM) in 12, low-grade non-Hodgkin lymphoma (NHL) in 6, multiple myeloma (MM) in 4, and chronic lymphocytic leukemia in 1 patient. Severe manifestations affected half the patients and were more frequent with IgG (82 vs. 30% (P = 0.006)). At last follow-up, 64% of patients had suffered no hematologic manifestation. Potent chemotherapeutic regimens were mainly used in HM. For patients with NMMG, WM, or NHL, fludarabine or rituximab-based regimens appeared to yield better responses. Five-year survival rate was 82%. In multivariate analysis, mortality was significantly higher in older patients (HR: 1.17 per year [95% CI: 1.06-1.28], P = 0.001) and those with nephropathy (HR: 8.9 [95% CI: 1.9-43], P = 0.006). Kidney disease, infections, Richter's transformation, and second malignancies were important sources of morbi-mortality. Despite its limitations, this series provide novel information regarding type 1 CG. Further studies are needed to improve its management. To date, therapeutic strategy should be tailored according to patient's characteristics (age, comorbidities, underlying BCD), and therapeutic target.
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PMID:Long-term outcome of monoclonal (type 1) cryoglobulinemia. 2453 35

We describe a case of a 59-year-old woman with a medical history of upper leg pain and chronic lymphatic leucaemia (CLL), with known diffuse bone marrow infiltration and without signs of lymphatic or extra-lymphatic disease activity on positron emission tomography CT (PET-CT). She presented with multiple fractures of the pelvis, sacrum and left proximal femur as a result of a low energy fall. During admission, she sustained a non-traumatic fracture of the right proximal femur. Pathological fractures in patients with CLL are usually based on Richter's transformation or multiple myeloma. However, in the current case, a PET-CT and a bone marrow biopsy showed no signs of this. We did see a normoparathyroid hypercalcaemia in our patient, most likely caused by a CLL-based release of local osteoclast stimulating factors. A combination of fludarabine/cyclofosfamide/rituximab was started as treatment in combination with allopurinol and sodium bicarbonate to prevent further osteolysis.
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PMID:Pathological fractures in a patient with chronic lymphatic leucaemia without disease progression. 2571 40

Richter's transformation (RT) is the transformation of chronic lymphocytic leukemia (CLL) into rapidly progressive B-cell lymphoma. This disease has long been recognized as a difficult-to-treat illness with poor survival outcomes. Although the incidence of RT has been well documented in previous studies, less is understood in the era of novel therapeutics, such as kinase inhibitors (KIs). The present review discusses the current risk factors, incidence, and outcomes of patients with RT in the modern era of KI therapy. Although the outcomes remain poor for RT patients after KI therapy, the most up-to-date studies have shown no increased incidence of RT in this patient population. Additionally, the present review reports the outcomes from the most recent data on novel therapies under investigation for patients with RT.
Clin Lymphoma Myeloma Leuk 2017 01
PMID:Richter's Transformation in the Era of Kinase Inhibitor Therapy: A Review. 2770 29


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