Subject(s)
Amyloidosis/drug therapy , Boronic Acids/therapeutic use , Immunoglobulin Light Chains , Pyrazines/therapeutic use , Adult , Aged , Bortezomib , Female , Humans , Indiana , Male , Middle AgedABSTRACT
Data on breast cancer resistance protein (BCRP, MXR, ABCG2) expression in acute myeloid leukemia (AML) have been inconsistent, possibly due to use of different assays in different studies. BCRP mRNA was studied by the reverse-transcription polymerase chain reaction and BCRP protein expression (BXP-21, BXP-34 or anti-ABCG2 antibody, with anti-CD34 and anti-CD33) and function (fumitremorgin C modulation of mitoxantrone retention) by flow cytometry in eight cell lines and in pretreatment blasts from 31 AML patients. BCRP mRNA levels, antibody staining and function correlated strongly in cell lines (Pearson r values, 0.73-0.97), but not in AML samples. AML sample BCRP mRNA levels were between those in parental 8226 and 35-fold mitoxantrone-resistant 8226/MR20 cells in all but one case, and BCRP mRNA had the wild-type sequence at codon 482 in all. In AML, unlike in cell lines, BCRP protein expression or function, when present, was only detected in small subpopulations. BCRP mRNA and protein expression did not correlate, nor did staining with different BCRP antibodies, and function did not correlate with mRNA nor protein expression. Presence of BCRP only in subpopulations and discordance among BCRP measurements suggest complex biology of BCRP in AML and incomplete modeling by cell lines.
Subject(s)
ATP-Binding Cassette Transporters/analysis , ATP-Binding Cassette Transporters/physiology , Leukemia, Myeloid/pathology , Neoplasm Proteins/analysis , Neoplasm Proteins/physiology , ATP Binding Cassette Transporter, Subfamily G, Member 2 , ATP-Binding Cassette Transporters/genetics , Acute Disease , Bone Marrow/pathology , Cell Line, Tumor , Drug Resistance, Multiple , Female , Flow Cytometry , Humans , Leukemia, Myeloid/metabolism , Mutation , Neoplasm Proteins/genetics , RNA, Messenger/analysis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Two macerated fetuses in utero are presented. The mothers experienced no abnormalities during pregnancy. Both fetuses were found postmortem to have intracranial angiomas. In case 1, the angioma in the choroid plexus of the right lateral ventricle was associated with intraventricular and subarchnoid hemorrhages. There was additional angiomatosis in the leptomeninges and substance of the brain. In case 2, there was leptomeningeal angiomatosis with diffuse subarchnoid hemorrhage. It is suggested that spontaneous rupture of the angioma of the choroid plexus in case 1 and of the leptomeninges in case 2 resulted in immediate death of the fetuses with subsequent maceration in utero. Asymptomatic angioma of the fourth ventricular choroid plexus is also described in case 2 because of its extreme rarity.
