NF-κB1 -94del/del ATTG polymorphic variant maintains CLL at an early, mildest stage.

BACKGROUND: NF-κB is an essential player in cancer biology, especially in tumor development, due to its constitutive activation, and because a four-base deletion (ATTG) in the NF-κB1 promoter region at site -94, alters mRNA stability and regulates translation efficiency. This polymorphism is a good candidate risk marker and modulator of clinical course in chronic lymphocytic leukemia (CLL). As the effect of this NF-κB1 gene polymorphism has not been studied in patients with CLL so far, the present study was undertaken to find out whether the NF-κB1 promoter -94 ins/del ATTG polymorphism might be an essential genetic risk factor and/or modulatory disease player associated with CLL. OBJECTIVES: The NF-κB1 -94 ins/del ATTG (rs28362491) polymorphism was investigated as a potential CLL susceptibility and progression factor, along with demonstration of potential modulation of the stage of clinical disease based on Rai classification. MATERIAL AND METHODS: The associations of NF-κB1 -94 ins/del ATTG polymorphism with CLL and its clinical manifestation in 282 Polish individuals, including 156 CLL patients, were analyzed using polymerase chain reaction (PCR) with primers including a labeled forward primer, followed by capillary electrophoresis. RESULTS: A higher occurrence of the del/del homozygosity was observed among patients when compared to controls, resulting in an increase in CLL risk of more than twofold in patients carrying this homozygous genotype (OR = 2.23, p = 0.02, 95% CI = 1.14-4.37). Moreover, the del/del-positive patients more frequently presented the less aggressive disease phenotype (Rai 0), suggesting a low probability of progression to more advanced disease. CONCLUSIONS: The NF-κB1 -94 del/del genetic variant, although associated with increased risk of CLL disease, may be associated with maintenance of disease severity in the early, mildest stage. The likelihood of disease progression may increase as the frequency of wild-type (insertion) alleles for this polymorphism increases.

Narrative review of aplastic anemia-the importance of supportive treatment.

Aplastic anemia (AA) is a rare, life-threatening syndrome of bone marrow failure resulted from bone marrow hypoplasia or aplasia, leading to pancytopenia (not only anemia). The most common cause is an autoimmune reaction of T lymphocytes against hematopoietic stem cells or, less frequently, a congenital defect or acquired damage to these cells, which leads to inhibition of their division and differentiation. AA can develop quickly (within a few days) or slowly (several weeks or months). The signs and symptoms are related to anemia, neutropenia, and thrombocytopenia. The concepts of treatment of patients with AA have significantly evolved in recent years. This is due to improved outcomes of both family and unrelated donor hematopoietic stem cell transplantations (HSCTs) as well as to revised results of immunosuppressive therapy (IST). The choice of the method depends essentially on three factors: the severity of AA, the age of the patient, matched sibling donor. All patients diagnosed with AA require appropriate supportive treatment adapted to the current clinical situation. Supportive treatment is necessary both before, during and after invasive causal treatment, it mainly involves the transfusion of leukocyte-depleted blood components, the use of anti-infectious prophylaxis or treatment of infections. In many cases AA, supportive therapy is the only therapeutic option, especially in elderly patients with comorbidities. In this paper we present current supportive treatment in this life-threatening disease.

The decrease in prolidase activity in myeloproliferative neoplasms.

BACKGROUND: The development of bone marrow fibrosis is a severe complication in hematological diseases. The progress of bone marrow myelofibrosis is evaluated by a trephine examination and may be characterized by the biochemical markers of collagen turnover determination. OBJECTIVES: Investigation of serum prolidase activity and biochemical markers of collagen metabolism in order to establish its role in the development of bone marrow fibrosis. MATERIAL AND METHODS: The group of 37 patients with myeloproliferative neoplasms (MPN) before treatment, consisted of 16 patients with chronic myeloid leukemia (CML), 7 with primary myelofibrosis (PMF), 8 with essential thrombocythopenia (ET), and 6 with polycythemia vera (PV). RESULTS: It was found that the plasma activity of prolidase (Pro) was reduced to almost half together with the serum level of osteocalcin (BGL), and hydroxyproline (H-PRO) in the serum and urine of patients with MPN in comparison to the control group. In the MPN group of patients, the levels of N-terminal procollagen III peptide (PIIINP), type I procollagen (PICP) and the C-terminal telopeptide of type I collagen (ICTP) were significantly higher. CONCLUSIONS: The alteration of collagen turnover markers in the MPN patient group (the elevation of synthesis and inhibition of collagen catabolism rate) has suggested that a diminished prolidase activity may contribute to such alteration of collagen metabolism and should be consider a biomarker of MPN progress.

[CIP and CAP fragments of parathormone and selected parameters of calcium-phosphate balance in patients with chronic kidney disease treated with repeated haemodialysis]. / Skladowe CAP i CIP czasteczki parathormonu a wybrane parametry gospodarki wapniowo-fosforowej u pacjentów z przewlekla choroba nerek leczonych powtarzanymi hemodializami.

INTRODUCTION: Chronic kidney disease (CKD) leads to bone and mineral complications, which are manifested, among others, by hyperparathyroidism, calcium-phosphate and vitamin D balance disturbances. The results of investigation assessing the usefulness of CAP/CIP ratio, (cyclase activating PTH/cyclase inactive PTH) as a marker of bone turnover and bone disturbances in this group of patients are contradictory. AIM OF THE STUDY: was to estimate the concentration of CAP and CIP of parathormone, connection with selected calcium-phosphate balance parameters and usefulness of CAP/CIP ratio to differentiate bone mineral density in patients with CKD treated with repeated haemodialysis. MATERIAL AND METHODS: The study included 31 children aged 5 to 18 years. Group I - 15 haemodialysed children. Group II - 16 healthy children. The patients underwent the following serum measurements: calcium concentration (Ca), inorganic phosphate (P), 1.25-dihydroxyvitamin D, parathormone (intact PTH), and CAP, CIP were evaluated with Scantibodies Laboratory Inc test. In group I the densitometric examination was done using the Lunar DPX-L system, performing the overall bone measurement. RESULTS: In children from group I the average values of iPTH concentration and both CIP and CAP components were significantly elevated (p<0.05) as compared to group II. CAP/CIP ratio in group I was <1; in healthy children >1. Average concentrations of Ca and 1.25(OH)2D in serum of group I were lowered, although without statistical significance in comparison with group II. CAP/CIP ratio does not differentiate the children with bone disturbances. Densitometric examination revealed osteopenic changes in 3 children and osteoporosis in 2 children. There were no statistically significant correlations between the examined parameters. CONCLUSIONS: 1. The CIP/CAP ratio does not differentiate the bone mineral density status and it is not associated with biochemical parameters of calcium-phosphate metabolism. 2. This indicates its poor diagnostic utility with reference to mineralization disturbances in children with chronic kidney disease.

Procollagen I carboxyterminal propeptide (PICP) as a bone formation marker and carboxyterminal telopeptide of type I collagen (ICTP) as a bone degradation marker in children with chronic renal failure under conservative therapy.

BACKGROUND: Biochemical and hormonal disturbances in calcium-phosphate storage accompanying chronic renal failure (CRF) lead to the loss of bone mass and the destruction of bone microarchitecture. The aim of this study was to evaluate the serum levels of PICP (procollagen I carboxyterminal propeptide) and ICTP (carboxyterminal telopeptide of type I collagen) as markers of bone growth in CRF children treated conservatively. MATERIAL/METHODS: 34 children (16 female and 18 males) with predialytic CRF, aged 6 to 18 years (average age 11.3+/-3.8 years) were included in the experimental group. The controls were 20 healthy age-matched children. The experimental subjects were divided into two subgroups, based on the blood level of intact PTH (iPTH). Subgroup Ia (n=7) consisted of children with normal serum concentrations of iPTH. Subgroup Ib (n=27) consisted of children with elevated serum concentrations of iPTH. RESULTS: In group Ia characteristic correlations were found between OST (osteocalcin) and ICTP, and between creatinine and ICTP. In group Ib, positive correlations were found between iPTH and PICP, iPTH and ICTP, OST and ICTP, and ICTP and PICP. In this group no correlation was found between marker turnover and creatinine. CONCLUSIONS: The results of our study of PICP and ICTP as markers of bone metabolism in children with CRF in the predialysis period indicate that their levels should be routinely monitored as specific biochemical parameters of bone structure.

[Usefulness of osteocalcin and CrossLaps as markers of bone turnover in children with chronic renal failure]. / Przydatnosc osteokalcyny i CrossLaps w ocenie zaburzen gospodarki kostnej u dzieci z przewlekla niewydolnoscia nerek leczonych zachowawczo.

UNLABELLED: Bone disorders resulting from abnormalities in mineral are common in patients with predialytic stage of chronic renal failure (CRF). Disturbances associated with: phosphate excretions, vitamin D3 metabolism, hypocalcemia, increased parathyroid hormone (PTH) and acid-base disturbances lead to bone pathology know as renal osteodystrophy (RO). Estimation of tempo turnover make possible markers, of which concentration means oneself in urine and in serum. The aim of this study was to estimate the urinary carboxy-terminal telopeptide of type I collagen as a index of bone resorption and osteocalcin as a marker of bone formation in correlation with intact PTH (iPTH) in predialytic children. The study group consisted of 39 children aged 6-17 y. All children were divided into 2 groups: I--21 predialytic pts; II--18 healthy children. The I group was divided into 2 subgroups: Ia--pts with normal range of iPTH; Ib--pts with higher range of iPTH. All patients were tested: for serum concentrations of: calcium (Ca), inorganic phosphorus (P), iPTH, OST; and for urinary CrossLaps (corrected with urinary creatinine). RESULTS: In subgroup Ib revealed correlation between OST and iPTH (p < 0.05); and between CrossLaps and OST (p = 0.05). CONCLUSIONS: The results of investigation on OST and CrossLaps as bone metabolism markers in predialytic children revealed that evaluating highly specific biochemical parameters of bone turnover is useful in assessing the clinical status of that metabolism. The knowledge of correlation between levels of bone turnover markers and clinical status of a child might help in taking appropriate therapeutic decision and in preventing renal osteodystrophy.

[Bone turnover markers in patients with leg ischemia before and after revascularization]. / Markery obrotu kostnego u pacjentów z niedokrwieniem konczyn przed i po rewaskularyzacji.

In patients with leg ischemia bone metabolism impairment has been observed. The aim of this study was to investigate the biochemical bone metabolism markers. Elevated level of osteolysis markers was observed before and 7 days after revascularization the level of markers was unchanged.