We present a case report of a patient with chronic
We present a case report of a patient with chronic myeloid leukemia (CML) who developed bilateral renal artery stenosis during tyrosine kinase inhibitor (TKI) therapy. Only a few reports associate TKIs with acute renal failure, and renovascular hypertension has not been previously described. Reports on peripheral artery occlusive disease occurring during nilotinib therapy have recently been published.
A 58-yr-old, nonsmoking, nondiabetic male patient with no history of cardiovascular disease or hypertension was diagnosed with CML in 2001. He was secondarily refractory to imatinib as a result of ABL mutations and developed a myeloid blast crisis in May 2006. Induction therapy with dasatinib was successful, leading to a major molecular remission, but in 2008, the patient had recurrent pleural effusions. The therapy was switched to 400mg nilotinib twice daily in April 2008.
The patient was hospitalized in August 2009 after a 6-month period of tinnitus, dizziness, headache, and vision disturbance. At the time of admission, his blood pressure was 260/140mmHg. An electrocardiogram (ECG) showed no signs of left ventricular hypertrophy, and an x-ray of the chest was normal. Ophthalmoscopy did not show hypertensive retinopathy. An echocardiography did not indicate any signs of left ventricular hypertrophy. A urinary dipstick was negative for protein.
Examination of the blood tests showed slightly decreased glomerular function with creatinine increasing from 104μmol/l to 160μmol/l (reference range 60–105μmol/l) in the first 5 days following admission. The patient started treatment with alpha and beta inhibitors, angiotensin-converting enzyme (ACE) inhibitor and calcium antagonists.
During hospitalization, the patient experienced dysarthria, hemianopsia and right-sided facialis nerve paresis. His blood pressure was 185/100mmHg. A computed tomography () scan of the Penciclovir Sodium showed an old infarction in the caudate nucleus and the internal capsula but no recent bleedings or infarctions. The patient started treatment with aspirin, dipyridamole and simvastatin.
Introduction Because lymphocytes of chronic lymphocytic leukemia (CLL) patients often fail to divide sufficiently in vitro, fluorescence in situ hybridization (FISH) probes have become a staple in the analysis of chromosomal aberrations in CLL (reviewed in Ref. 1). In a groundbreaking study, a FISH probe panel was used to classify CLL patients into one of five prognostic groups, with the poorest prognosis seen in patients with deletion of 17p13.1 (site of TP53), followed by loss of 11q22.3 (ATM), trisomy 12 and normal FISH results, whereas patients with del(13q14) as the only alteration had the most favorable prognosis. Although FISH analysis is now widely used for the cytogenetic assessment of CLL, other approaches such as oligonucleotide-based array comparative genomic hybridization and single nucleotide polymorphism (SNP) gene chips show comparable results, but also assess all chromosomal regions rather than the current standard clinical practice of identifying alterations with probes targeting only 4–5 chromosomal sites. The high-resolution gene copy number analysis afforded by DNA arrays provides greater precision in demarcating boundaries of individual genomic imbalances and uncovers alterations overlooked by FISH analysis. In this report, we describe cytogenetic findings in a CLL case with del(17p13.1) by FISH in which SNP arrays detected profound genomic upheaval due to chromothripsis, a phenomenon by which a specific region(s) of the cancer genome is shattered into pieces and then recombined via a single devastating event, generating frequent oscillations between two DNA copy number states, that may lead to malignant transformation.
Materials and methods Karyotypic analysis was performed on a blood sample cultured for 24h. FISH analysis was performed using Abbott\'s Vysis CLL FISH Probe Kit. DNA copy number and allele analysis were performed as described in detail elsewhere. Briefly, total genomic DNA from blood was Nsp-digested, ligated with an adaptor complimentary to PCR primer, PCR amplified, purified, fragmented, biotin labeled, and hybridized to an Affymetrix CytoScan HD array, according to the manufacturer\'s protocol. The hybridized array was washed and then scanned with a GeneChip Scanner 3000 7G prior to data analysis.