Yuksel Pekcelen

P‐selectin glycoprotein ligand‐1 VNTR polymorphisms and risk of thrombosis in the antiphospholipid syndrome

Objectives: Antiphospholipid antibodies (aPLA) have been shown to enhance thrombus formation by increasing the expression of adhesive receptors such as P-selectin on endothelial cells. The P-selectin counter-receptor on leucocytes is P-selectin glycoprotein ligand-1 (PSGL-1). We have previously described a variable number of tandem repeats (VNTR) polymorphism in the mucin-like region of PSGL-1, with three alleles: allele A, 16 repeats; allele B, 15 repeats; and allele C, 14 repeats. Methods: We compared the PSGL-1 VNTR allele and genotype frequencies in 90 patients with antiphospholipid syndrome (APS) with thrombosis, 39 patients with persistent aPLA positivity without thrombosis, and 203 healthy controls. Results: The frequency of the B allele was significantly higher in patients with APS with thrombosis compared with patients without thrombosis (p = 0.023). When we compared the groups by genotype frequencies, we found a markedly higher frequency of the AB genotype in patients with APS with thrombosis than in aPLA-positive patients without thrombosis (38.9% vs 10.3%, p = 0.001) or in normal population (38.9% vs 22.2%, p<0.01). Conclusions: We suggest that the VNTR polymorphism of PSGL-1 is a significant determinant of thrombotic predisposition in patients with APS. Furthermore, risk appears to correlate best with the combination of alleles inherited rather than with the presence of any particular allele.

Factor XIII Val34Leu polymorphism does not contribute to the prevention of thrombotic complications in patients with antiphospholipid syndrome

The effect of thrombophilic mutations in the development of thrombosis in patients with antiphospholipid syndrome (APS) has been extensively investigated. Factor XIII (FXIII) Val34Leu polymorphism is a newly described polymorphism which is located in the three amino acids away from the thrombin activation site of the FXIII-A subunit. It has been reported that the Leu allele decreases the risk of both arterial and venous thrombosis. In the present study, we examined the associationbetween the FXIII Val34Leu polymorphismand the developmentof thrombosisin patients with APS. Sixty APS patients with arterial and venous thrombosis, 22 antiphospholipid antibody (aPLA) positive patients with first trimester abortus and/or thrombocytopenia,126 healthy controls, and 60 healthy subjects who were age- and sex-matched with thrombotic APS group were included into the study. FXIII Leu allele frequencies in the APS patients with thrombosis, aPLA-positive patients without thrombosis, healthy controls, and matched controls were 13.3, 16, 19.5, and 18.3%, respectively. When we compared Leu allele frequencies between APS patients with thrombosis and aPLA-positive patients without thrombosis, healthy controls or matched controls, we could not find any difference (x 2, P 0.43, and P 0.09, P 0.67, respectively). Our results showed that the FXIII Leu allele has no protectiveeffect in the developmentof thrombosis in APS.

47,XYY Karyotype in Acute Myeloid Leukemia

A case of acute myelomonocytic leukemia (AMMoL; M4) with a 47,XYY karyotype is reported. This chromosome aneuploidy was found in both bone marrow cells and mitogen-stimulated lymphocytes. The contribution of XYY chromosomal constitution in the pathogenesis of AMMoL is controversial.

Bullous acral erythema and concomitant pigmentation on the face and occluded skin

To the Editor We report a patient with acute myeloid leukaemia who concomitantly developed bullous acral erythema of the hands and hyperpigmentation during chemotherapy with daunorubicin, cyclosporin and high dose cytarabine. Although hyperpigmentation is well known after daunorubicin and cyclosporin, and bullous acral erythema after cytarabine, the combined occurrence of the two conditions due to cytarabine, daunorubicin or cyclosporin has not been reported before. A 38-year-old caucasian woman with acute myeloid leukaemia (AML-M4) was on the fourth cycle of a combination chemotherapy. She was treated with cyclosporin A 2.5-mg/kg on days 0, 1, 2, 3 and 7, 8, 9, 10; cytarabine 2 g/m 2 on days 1, 2, 3; daunorubicin 50 mg/m 2 on days 1, 2, 3 and etoposide 200 mg/m 2 on days 8, 9, 10. On the second day of this chemotherapy regimen, painful erythema occurred on palmar surfaces of both hands, followed by involvement of the dorsum of the hands within 48 h. The eruption soon became purpuric and hyperpigmented; it progressed to severe oedema and bullae within a few days (fig. 1). Concomitantly, an erythematous eruption developed and evolved into a peculiar hyperpigmentation that was intense on the face (fig. 2), intertriginous areas such as neck, submammary and inguinal regions, and on skin occluded by adhesive tape. Total alopecia and severe mucositis accompanied the lesions. The acral erythema healed with desquamation and shedding of the fingernails within 4 weeks and the hyperpigmentation regressed completely within 6 weeks. Histopathological examination of the punch biopsy material obtained from the dorsal surface of the left hand revealed interface dermatitis with diffuse vacuolar degeneration of basal keratinocytes, numerous dyskeratotic cells, mild acanthosis, pigmentary incontinence and mild perivascular inflammatory infiltration consisting of lymphomonocytes on the upper dermis; all of which supported the diagnosis of bullous acral erythema. Acute graft vs. host disease was excluded because there had been no bone marrow transplantation or blood transfusions. There were no signs of vessel wall damage or eccrine sweat gland/duct changes. No punch biopsy material could be obtained from the hyperpigmented lesions. Chemotherapy-induced acral erythema (CAE) is an uncommon and self-limited localized cutaneous reaction in patients receiving systemic chemotherapy that is characterized by painful, symmetric, well-defined swelling and erythema predominantly on the palms and sometimes also on the soles. 1

A Case of Chronic Lymphocytic Leukemia with a Constitutional Pericentric Inversion of Chromosome 1

Chronic lymphocytic leukemia (CLL) has been reported to be associated with various chromosomal aberrations, the most common being trisomy 12 and structural rearrangements involving 13q, 11q, and 17p. We present a case of CLL with a constitutional pericentric inversion of chromosome 1.

Comparison of the cytogenetic and molecular analyses in the assessment of imatinib response in chronic myelocytic leukemia.

We aimed to compare the cytogenetic and molecular analyses in the assessment of imatinib mesylate response in patients suffering the chronic phase of chronic myelocytic leukemia who were refractory to alpha-interferon treatment. A total of 117 patients in the chronic phase of chronic myelocytic leukemia were included. The patients were treated with 400 mg/day imatinib mesylate. Bone marrow samples were obtained for the cytogenetic and molecular analyses. Patients without the Ph chromosome were defined as complete cytogenetic responders. Partial cytogenetic response was determined when the Ph chromosome was detected in 1-35% of the cells. Molecular response was determined by quantitative real-time reverse transcriptase polymerase chain reaction (QR-PCR) and defined as no detection of BCR-ABL mRNA. The frequencies of complete and partial cytogenetic response were 29% (n = 34) and 15% (n = 18), respectively. No cytogenetic response was achieved in 56% (n = 65) of the patients. Molecular response was achieved in 62% (n = 21) and 33% (n = 6) of the complete and partial cytogenetic responders, respectively. All of the 65 patients with no cytogenetic response were also molecular nonresponders. We conclude that there is reasonable agreement between the cytogenetic and molecular analyses. Both methods are complementary in the assessment of response to therapy.