846P Predictive and prognostic values of serum VEGF in patients with multiple myelomas receiving bortezomib-based therapy

Multiple myeloma (MM) is a type of cancer characterized by abnormal proliferation of clonal cells; it is the very dangerous and highly prevalent disease. Although significant progress has been made in clinical research, especially with novel drugs such as bortezomib, lenalidomide, and carfilzomib, most of the patients with MM still suffer from often fetal relapses due to drug resistance. In this study, we aimed to develop immune cells that could specifically target and destroy MM cells. Chimeric antigen receptor–modified NK-92 (CAR-NK92) cells have been very effective against B-cell acute lymphoblastic leukemia (B-ALL); as MM shows high expression of CD138, we constructed CD138-directed CAR-NK-92MI cells (CAR-CD138). It 2is reported that there is a small subset of CD138–/CD19+ MM cells showing, to some extent, stem cell qualities. We therefore generated the CD19-directed CAR-NK-92MI cells (CAR-CD19) as well. These two CAR-NK cells showed strong in vitro biological activity in specifically killing target tumor cells. Thus, the concomitant use of these CAR-NK cells may achieve excellent results in vivo.

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MicroRNAs as Haematopoiesis Regulators

Advances in Hematology ◽

10.1155/2013/695754 ◽

2013 ◽

Vol 2013 ◽

pp. 1-20 ◽

Cited By ~ 46

Author(s):

Ram Babu Undi ◽

Ravinder Kandi ◽

Ravi Kumar Gutti

Keyword(s):

Blood Cells ◽

Erythroid Differentiation ◽

Lymphocytic Leukemia ◽

Myelogenous Leukemia ◽

Aberrant Expression ◽

Hematopoietic Stem ◽

Complex Process ◽

Development And Differentiation ◽

Multiple Myelomas

The production of different types of blood cells including their formation, development, and differentiation is collectively known as haematopoiesis. Blood cells are divided into three lineages erythriod (erythrocytes), lymphoid (B and T cells), and myeloid (granulocytes, megakaryocytes, and macrophages). Haematopoiesis is a complex process regulated by several mechanisms including microRNAs (miRNAs). miRNAs are small RNAs which regulate the expression of a number of genes involved in commitment and differentiation of hematopoietic stem cells. Evidence shows that miRNAs play an important role in haematopoiesis; for example, myeloid and erythroid differentiation is blocked by the overexpression of miR-15a. miR-221, miR-222, and miR-24 inhibit the erythropoiesis, whereas miR-150 plays a role in B and T cell differentiation. miR-146 and miR-10a are downregulated in megakaryopoiesis. Aberrant expression of miRNAs was observed in hematological malignancies including chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myelomas, and B cell lymphomas. In this review we have focused on discussing the role of miRNA in haematopoiesis.

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Electron microscope studies on renal biopsies from patients with ischaemic anuria, lipoid nephrosis, multiple myelomas and diabetes mellitus

Verhandlungen Band II / Biologisch-Medizinischer Teil ◽

10.1007/978-3-662-22058-0_98 ◽

1960 ◽

pp. 396-399

Author(s):

Ole Z. Dalgaard

Keyword(s):

Diabetes Mellitus ◽

Electron Microscope ◽

Renal Biopsies ◽

Multiple Myelomas

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Pathological Rupture of the Spleen in Uncomplicated Myeloma

Clinical Medicine Case Reports ◽

10.4137/ccrep.s725 ◽

2008 ◽

Vol 1 ◽

pp. CCRep.S725 ◽

Cited By ~ 1

Author(s):

Vincent Ho ◽

Andrew Shearer ◽

Mark Jagusch

Keyword(s):

Multiple Myeloma ◽

Plasma Cell ◽

Splenic Rupture ◽

Uneventful Recovery ◽

Pathophysiological Mechanisms ◽

Similar Tendency ◽

Multiple Myelomas ◽

Rupture Of The Spleen

Pathological rupture of the spleen in uncomplicated myeloma is extremely rare. We present a case of a splenic rupture which occurred in a 52 year old woman with uncomplicated multiple myeloma. The patient required an urgent splenectomy and had an uneventful recovery. Pathophysiological mechanisms leading to splenic rupture are discussed. Plasma cell leukaemias have been previously documented to present with splenic rupture. A subgroup of aggressive multiple myelomas such as in our case may have a similar tendency for splenic rupture.

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A Retrospective Analysis: A Novel Index Predicts Survival and Risk-Stratification for Bone Destruction in 419 Newly Diagnosed Multiple Myelomas

OncoTargets and Therapy ◽

10.2147/ott.s229122 ◽

2019 ◽

Vol Volume 12 ◽

pp. 10587-10596

Author(s):

Yanxia Jin ◽

Yufeng Shang ◽

Hailing Liu ◽

Lu Ding ◽

Xiqin Tong ◽

...

Keyword(s):

Risk Stratification ◽

Retrospective Analysis ◽

Bone Destruction ◽

Newly Diagnosed ◽

Multiple Myelomas

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Hypercalcemia as a Cause of Kidney Failure: Case Report

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2016.044 ◽

2016 ◽

Vol 4 (2) ◽

pp. 283-286

Author(s):

Olivera Stojceva-Taneva ◽

Borjanka Taneva ◽

Gjulsen Selim

Keyword(s):

Renal Failure ◽

Primary Hyperparathyroidism ◽

Epigastric Pain ◽

History Of ◽

St Elevation ◽

Multiple Myelomas ◽

Serum Pth ◽

Reduced Kidney Function ◽

Common Manifestation ◽

Pth Level

BACKGROUND: Hypercalcemia is a common manifestation in clinical practice and occurs as a result of primary hyperparathyroidism, malignancy, milk-alkali syndrome, hyper or hypothyroidism, sarcoidosis and other known and unknown causes. Patients with milk-alkali syndrome typically are presented with renal failure, hypercalcemia, and metabolic alkalosis caused by the ingestion of calcium and absorbable alkali. This syndrome is caused by high intake of milk and sodium bicarbonate.CASE PRESENTATION: We present a 28-year old male admitted to hospital with a one-month history of nausea, vomiting, epigastric pain, increased blood pressure and worsening of renal function with hypercalcemia. His serum PTH level was almost undetectable; he had mild alkalosis, renal failure with eGFR of 42 ml/min, anemia, hypertension and abnormal ECG with shortened QT interval and ST elevation in V1-V4. He had a positive medical history for calcium-containing antacids intake and after ruling out primary hyperparathyroidism, malignancy, multiple myelomas, sarcoidosis, and thyroid dysfunction, it seemed plausible to diagnose him as having the milk-alkali syndrome.CONCLUSION: Although milk-alkali syndrome currently may be more probably a result of calcium and vitamin D intake in postmenopausal women, or in elderly men with reduced kidney function taking calcium-containing medications, one should not exclude the possibility of its appearance in younger patients taking calcium-containing medications and consider it a serious condition taking into account its possibility of inducing renal insufficiency.

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Analysis of VH gene expression in CD5+ and CD5- B-cell chronic lymphocytic leukemia

Blood ◽

10.1182/blood.v86.10.3883.bloodjournal86103883 ◽

1995 ◽

Vol 86 (10) ◽

pp. 3883-3890 ◽

Cited By ~ 23

Author(s):

K Maloum ◽

F Davi ◽

C Magnac ◽

O Pritsch ◽

E McIntyre ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Random Distribution ◽

Lymphocytic Leukemia ◽

Mutation Pattern ◽

Vh Gene ◽

Vh Genes ◽

Multiple Myelomas ◽

Differentiation Stage ◽

Follicular Lymphomas

In contrast to highly mutated follicular lymphomas and multiple myelomas, chronic lymphocytic leukemias (CLLs) frequently express VH genes in germline configuration. It is currently unclear whether this difference is related to the expression of CD5 or to the differentiation stage of the B cell when malignant transformation occurs. We have studied the VH sequence of 11 cases of CD5- B-CLL to address the question whether CD5- B-CLL are derived from naive pregerminal B cells (low mutation pattern) or from germinal center- derived memory B cells (high mutation pattern). Among the 12 detected rearrangements (2 distinct rearrangements in 1 case) VH1 family was found in 2, VH2 in 2, VH3 in 4, and VH4 in 4. Nine different VH genes were detected among the 12 rearrangements, including 2 cases expressing V1–69 (51p1) and 1 case expressing V4–39 (VH4.18), previously reported to be overexpressed in CD5+ B-CLL. A higher mutation pattern, following a random distribution, was observed when compared with classical CD5+ B- CLL. However, as reported in normal B cells, these results appeared to be related to membrane Ig phenotype (less mutations in membrane mu delta-expressing forms in leukemias expressing exclusively membrane mu). Overall, the differences found when comparing the mutational profile with classical CD5+ B-CLL were not clearcut and might be explained more by the membrane isotype (mu v mu delta) than by CD5 expression.

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Light Chain Predominant Intact Immunoglobulin Monoclonal Gammopathy Disorders: Shorter Survival in Light Chain Predominant Multiple Myelomas

Laboratory Medicine ◽

10.1093/labmed/lmaa057 ◽

2020 ◽

Author(s):

Gurmukh Singh ◽

Hongyan Xu

Keyword(s):

Plasma Cell ◽

Light Chain ◽

Change Point ◽

Monoclonal Gammopathy ◽

Biological Significance ◽

Data Set ◽

Serum Free ◽

Associated Lesions ◽

Multiple Myelomas ◽

Undetermined Significance

Abstract Background A proportion of intact immunoglobulin (Ig)–producing multiple myelomas (MMs) was observed to secrete much higher amounts of free light chains (LCs) than usual. Objectives To determine the change point between usual and LC-predominant intact Ig-secreting MMs and other monoclonal gammopathic manifestations and the biological significance of the observation. Methods We conducted retrospective examination of laboratory findings in 386 MM, 27 smoldering MM, and 179 monoclonal gammopathy of undetermined significance (MGUS) cases that secreted intact Igs. We recorded the highest levels of involved serum free LC, highest ratio of involved to uninvolved LC, highest concentration of involved LC per g of monoclonal Ig, and highest value for ratio of involved to uninvolved LCs divided by the monoclonal Ig concentration. Each data set was sorted into kappa- and lambda LC-associated lesions. Length of time, in months, between diagnosis and last contact with the patients having myeloma was recorded. Results Change point analysis of data revealed a subgroup of cases with distinctly higher levels of free LCs. In myelomas, including plasma cell leukemias, 16.4% of myelomas with kappa LCs and 22.3% of myelomas with lambda LCs, the LC secretion was distinctly higher than in the remaining cases, by a combination of 4 parameters, listed herein. Corresponding figures for smoldering myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) were 12.5, 27.3, 3.8, and 6.8, respectively. Ten of the 13 (77%) cases of plasma cell leukemia) and all cases of IgD myeloma (n = 4) showed excess secretion of serum free LCs. Among IgG and IgA myelomas, including plasma cell leukemias, the LC-predominant lesions had shorter survival, by an average of 22.5 months. Conclusions In total, 18.4% of MMs, including plasma cell leukemias, secrete distinctly higher amounts of serum free LCs than other intact Ig-secreting myelomas and confer significantly lower survival. Quantification of monoclonal serum free LCs may be useful in this subgroup in monitoring progress and potentially in ascertaining minimal residual disease. The findings also stress the need for separate criteria for kappa and lambda LC associated monoclonal gammopathic manifestations. The significantly shorter survival of patients with LC-predominant myelomas warrants consideration in prospective trials of treatments.

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