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URL http://www.rockymountainbmt.com/news/A-new-study-quotThe-CML-related-oncoprotein-BCRABL-induces-expression-of-histidine-decarboxylase-HDC-and-the-synthesis-of-histamine-in-leukemic-cellsquot-is-now-available-9830.html

A new study, "The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells," is now available

02-26-2007

According to a study from Vienna, Austria, "Basophil numbers are typically elevated in chronic myeloid leukemia (CML) and increase during disease progression. Histamine is an essential mediator and marker of basophils and is highly up-regulated in CML."

"We examined the biochemical basis of histamine synthesis in CML cells. The CML-specific oncoprotein BCR/ABL was found to promote expression of histidine decarboxylase (HDC) and synthesis of histamine in Ba/F3 cells. Moreover, the BCR/ABL tyrosine kinase inhibitors imatinib (STI571) and nilotinib (AMN107) decreased histamine levels and HDC mRNA expression in BCR/ABL-transformed Ba/F3 cells, in the CML-derived basophil cell line KU812, and in primary CML cells. Synthesis of histamine was found to be restricted to the basophil compartment of the CML clone and to depend on signaling through the PI3-kinase pathway. CML cells also expressed histamine receptors (HRs), including HR-1, HR-2, HR-4, and histamine-binding CYP450 isoenzymes which also serve as targets of HR antagonists. The HR-1 antagonists loratadine and terfenadine, which bind to CYP450, were found to counteract proliferation of CML cells, whereas no growth inhibition was observed with the HR-1 antagonist fexofenadine which is not targeted or metabolized by CYP450. Moreover, DPPE, an inhibitor of histamine-binding CYP450 isoenzymes, produced growth inhibition in CML cells," wrote K.J. Aichberger and colleagues, Medical University of Vienna, Division of Hematology and Hemostaseology.

The researchers concluded: "Together, these data show that BCR/ABL promotes histamine production in CML cells and that certain HR-targeting drugs exert antileukemic effects on CML cells."

Aichberger and colleagues published their study in Blood (The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells. Blood, 2006;108(10):3538-47).

For more information, contact K.J. Aichberger, Medical University of Vienna, Medical University of Vienna, Division of Hematology and Hemostaseology, AKH-Wien, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

This article was prepared by Surgery Litigation & Law Week editors from staff and other reports. Copyright 2007, Surgery Litigation & Law Week via NewsRx.com.