Effect of 1,25(OH)2 Vitamin D3 analogs on differentiation induction and cytokine modulation in blasts from acute myeloid leukemia patients

Leukemia & Lymphoma
Maya D Srivastava, Julian L Ambrus

Abstract

In acute myeloid leukemia (AML), cell proliferation and differentiation are uncoupled, causing a maturation block. Induction of terminal differentiation is a potential therapeutic strategy. 1alpha, 25(OH)2 Vitamin D3 regulates differentiation and is immunomodulatory at concentrations causing severe hypercalcemia, thus limiting its use. We investigated 1alpha, 25(OH)2 Vitamin D3 and 5 of its more potent analogs with reduced calcium resorbing activity for differentiation of blast cells from AML (FAB M1) patients, compared to TPA. Blast phenotype, p-glycoprotein expression, cytokine production, and lineage specificity were examined. The Vitamin D3 analogs had no effect on cell viability and proliferation. They induced incomplete differentiation, with increase in AP, NSE and NBT positivity of cells, but no cell sticking and spreading as observed with TPA. The analogs were more effective than the parent compound. They also inhibited the production of IL-6 and IL-8. Vitamin D3 and its analogs can induce differentiation of primary cells from AML patients in vitro, but may need to be combined with other agents for terminal differentiation of blasts and effective therapy in vivo.

References

Sep 15, 1988·International Journal of Cancer. Journal International Du Cancer·R J ScheperJ Lankelma
May 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·H ReichelA W Norman
Aug 1, 1994·Mutation Research·A F McFeeM D Shelby
Jul 1, 1996·European Journal of Haematology·I OlssonU Gullberg
Dec 19, 1998·Annals of Hematology·V GatteiA Pinto
May 19, 2001·The Journal of Steroid Biochemistry and Molecular Biology·C M HansenL Binderup
Jun 26, 2001·The Oncologist·M J Mauro, B J Druker
Aug 16, 2001·Journal of the National Cancer Institute·M DanilenkoG P Studzinski
Mar 28, 2002·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·H BartelinkM van Glabbeke
Aug 22, 2002·International Immunopharmacology·Luciano Adorini
Aug 30, 2002·British Journal of Haematology·Hakan SavliSeppo Pakkala
Nov 9, 2002·Medicinal Research Reviews·Sachiko YamadaKeiko Yamamoto
Feb 4, 2003·Nature Reviews. Cancer·Daniel G Tenen

❮ Previous
Next ❯

Citations

Jul 1, 2009·Journal of Periodontology·Kaining LiuRuifang Lu
Feb 23, 2017·International Journal of Cancer. Journal International Du Cancer·Ju Han SongTae Sung Kim

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

CNS Lymphoma

In CNS lymphoma, cancerous cells from lymph tissues or other parts of the body form tumors in the brain and/or spinal cord. Here is the latest research on this rare non-Hodgkin lymphoma.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

Related Papers

The Journal of Steroid Biochemistry and Molecular Biology
J L DavideauA Berdal
Mini Reviews in Medicinal Chemistry
Ying K YeeSunil Nagpal
Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
J J ChenB D Boyan
© 2021 Meta ULC. All rights reserved