Correlation between smoking and downregulation of red cell CD47 as eryptosis marker.

OBJECTIVE: The purpose of this research is to discover a link between cigarette smoking and decreased red cell CD47 expression. SUBJECTS AND METHODS: The current cross-sectional study included 72 smokers (who had smoked 20 cigarettes per day for at least two years) and 50 nonsmokers, as well as nonsmokers who had not been exposed to smokers on a regular basis and chose to participate as controls. Due to exclusion criteria, 11 participants were removed from the study; they had various genetic, immune, and metabolic disorders, leaving only 61 healthy people in the study. A flow cytometer was used to examine CD47. RESULTS: There was a strong correlation between smoking and a decrease in CD47 markers in all types of smokers in the control samples (p-value = 0.000), as well as among cigarette smokers only (p-value = 0.000), cigarette and Shisha smokers (p-value = 0.024), and cigarette and e-cigarette smokers (p-value = 0.014). Furthermore, there is a strong correlation between the appearance of the CD47 marker in healthy smokers and smokers with non-hereditary blood diseases like iron deficiency anemia and polycythemia. CONCLUSIONS: It can be concluded that smoking significantly reduces the expression of the CD47 marker.

Warm autoimmune hemolytic anemia with mimicking anti-c and -E specificities.

An 18-month-old male was admitted to a hospital with a hemoglobin of 4.1 g/dL and a reticulocyte count of 53 percent. There was no history of prior transfusion. Serologic evaluation revealed the presence of both a positive direct antiglobulin test (DAT) and an indirect antiglobulin test (IAT). The patient's red blood cells (RBCs) typed as group A, C-D-E-c+e+ (cde/cde). Evaluation of the IAT revealed the presence of anti-c and anti-E. All other major antibodies were ruled out. Upon adsorption of the patient's serum with ficin-treated Cde/Cde RBCs, both antibody specificities were adsorbed; however, the antibodies were not adsorbed with native (untreated) Cde/Cde RBCs. Furthermore, the autoantibody was not adsorbed by Rhnull cells, thereby suggesting Rh specificity. The serum was incompatible with cde/cde RBCs and compatible with Cde/Cde RBCs. The patient was successfully transfused with Cde/Cde RBCs followed by resolution of his anemia, as evidenced by an increased and stable hemoglobin. It was concluded that the autoantibody had mimicking anti-c and -E specificities. This is a report of an unusual case of autoimmune hemolytic anemia because the Rh autoantibody appeared to have dual mimicking specificities, and the patient's RBCs were antigen negative for one of the antibody specificities, i.e., anti-E.

Prevalence of myeloperoxidase gene expression in infant acute lymphocytic leukemia.

The enzyme myeloperoxidase (MPO; donor: H2O2 oxidoreductase, EC1.11.1.7) is a well-established marker of myeloid differentiation. Most myeloid leukemias express MPO enzyme activity at the light microscopic level, whereas lymphoid leukemias characteristically lack such expression. However, the diagnostic significance of MPO RNA expression or of immunohistochemically detectable MPO protein expression in leukemic blasts is unclear. We studied the prevalence and diagnostic significance of MPO RNA and protein expression in 57 cases of MPO enzyme-negative infant B-precursor acute lymphocytic leukemia (ALL), since the blast cells in this condition have been reported to show a high incidence of coexpression of myeloid-associated antigens. MPO expression was compared with other clinical and laboratory parameters. Of the cases examined, 56% showed detectable MPO expression at the RNA or protein level or both. Most positive cases showed MPO protein in many leukemic blasts, whereas a few cases showed substantial MPO protein expression in only a few blast cells. MPO expression showed no significant correlation with other markers of myeloid differentiation. Leukemic lymphoblasts in infant ALL frequently express MPO at the RNA or protein level; this expression does not imply an overall myeloid phenotype. The leukemic blasts in infant ALL may derive from an immature hematopoietic precursor cell not fully committed to lymphoid differentiation.

Lack of ETV6 (TEL) gene rearrangements or p16INK4A/p15INK4B homozygous gene deletions in infant acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) occurring in infants less than 1 year of age differs clinically and biologically from that observed in older children. Cytogenetically, 11q23 translocations are detected in approximately 50% of infant ALLs and fuse the 11q23 gene HRX with a variety of partner chromosomal loci. Overall, HRX rearrangements are detected molecularly in 70-80% of infant ALLs as compared to 5-7% of ALLs arising in older children. Two recently described molecular abnormalities in childhood ALL are ETV6 gene rearrangements and homozygous deletions of p16(INK4A) and/or p15(INK4B). Each of these abnormalities occurs in 15-20% of all childhood ALLs, and neither can be accurately identified by routine cytogenetic analyses. The incidence of these genetic abnormalities and their potential relationship to HRX gene status in infant ALL is unknown. Using Southern blot analyses, we determined ETV6 and p16(INK4A)/p15(INK4B) gene status in a cohort of infant ALLs. No ETV6 rearrangements or homozygous deletions (n=69) or homozygous p16(INK4A) and/or p15(INK4B) gene deletions (n=54) were detected in any of the infant ALLs. Therefore, ETV6 and p16(INK4A)/p15(INK4B) do not play a significant role in the pathogenesis of infant ALL, further emphasizing the distinctive biology of this subset of leukemias.

Frequency and prognostic significance of HRX rearrangements in infant acute lymphoblastic leukemia: a Pediatric Oncology Group study.

Chromosome band 11q23, the location of the HRX gene, is a site of recurrent translocations in human malignancies. Infants with acute lymphoblastic leukemia (ALL) commonly have 11q23 translocations and have an especially poor prognosis despite intensive chemotherapy. We analyzed 96 cases of infant ALL treated on three consecutive Pediatric Oncology Group protocols to determine the frequency and prognostic significance of molecular rearrangements of HRX. Overall, 78 cases (81%) had HRX rearrangements detected by Southern blot analysis performed with a single HRX cDNA probe, whereas 18 cases (19%) had germline HRX. Of the 78 cases with HRX rearrangements, only 50 had abnormalities of 11q23 detected cytogenetically. Molecular abnormalities of HRX were associated with early treatment failure and a very poor outcome. Estimated event-free survival for patients with HRX rearrangements was 19% (SE, 7%) at 3 years, compared with 46% (SE, 17%) for patients with germline HRX (P = .033 by the two-sided logrank test). Therefore, infants with ALL and molecular abnormalities of HRX represent a group with an extremely high rate of failure who clearly need innovative or experimental treatment. Furthermore, cytogenetic analysis alone failed to detected 36% of HRX rearrangements, suggesting that molecular analysis be performed on all infants with ALL to identify this group of high-risk patients.

Acute nonlymphocytic leukemia in children.

Acute nonlymphocytic leukemia (ANLL) is a heterogeneous group of hematologic malignancies caused by a clonal proliferation of primitive myeloid cells. 30 Infiltration of the bone marrow by these cells causes impairment of normal hematopoiesis and results in anemia, granulocytopenia, and thrombocytopenia. Recent progress in bone marrow culture techniques, cytogenetics, and immunology have contributed to a better understanding of the pathophysiology of ANLL. Major therapeutic advances have also occurred because of improved supportive care and carefully designed prospective and randomized clinical trials. This article presents the current knowledge of the diagnosis and management of ANLL.

Combined etoposide and 5-azacitidine in children and adolescents with refractory or relapsed acute nonlymphocytic leukemia: a Pediatric Oncology Group Study.

An intensive regimen of combined etoposide (VP-16) and 5-azacitidine (5-Az) was used to treat 96 children and adolescents with refractory or relapsed acute nonlymphocytic leukemia (ANLL). Patients were given two sequential five-day courses of VP-16, 250 mg/m2 for three days, followed by 5-Az, 300 mg/m2 for two days. An additional five-day course was administered if marrow aplasia was not evident by day 13. A complete remission rate of 45% was achieved with a median of two courses of VP-16 and 5-Az. The outcome of induction therapy was not influenced by prior treatment, blast cell morphology, or disease status on study entry (refractory or relapsed). Twenty-seven patients have relapsed after remission periods of 35 to 920 days (median, 110 days); seven others are free of leukemia for up to 519 days. The effectiveness of VP-16/5-Az combination therapy in patients refractory to anthracyclines and cytarabine indicates a potential role for these compounds in first-line treatment of patients with ANLL.

Alterations of HLe-1 (T200) fluorescence intensity on acute lymphoblastic leukemia cells may relate to therapeutic outcome.

Quantitative differences in HLe-1 expression were studied on normal lymphocytes and lymphoblasts of patients with acute lymphoblastic leukemia (ALL). A relationship was found between quantitative antigen expression and therapeutic outcome. Alterations in fluorescence intensity (FI) were demonstrated using quantitative flow cytometric methods and the monoclonal antibody (MoAb) anti HLe-1 (T200). Lymphoblasts from patients with ALL produced FI peaks ranging form channel 17 to 112 (mean 68; n = 28), while normal lymphoid cells were at FI channel 127 +/- 3 (n = 121). Patients with the dimmest-staining lymphoblasts (channels 17-50) responded better to therapy than those with brighter-staining cells (channels 50-100). Data from this pilot study suggests that the FI of malignant lymphoblasts has implications in the clinical response to therapy.

Translocation (4;11) in acute myelogenous leukemia.

A child with acute myelogenous leukemia is presented. Cytogenetic analysis of her leukemic cells revealed a (4;11)(q12;q23) translocation. The slight difference in the breakpoint on chromosome #4 from previously reported cases of t(4;11) may account for the degree of myeloid differentiation expressed. Acute leukemia associated with t(4;11) is a unique subgroup that originates in an early myeloid stem cell and carries a poor prognosis.

Pseudotumor of hemophilia in the orbit: the role of radiotherapy in management.

A case of pseudotumor of hemophilia is presented that occurred in the right orbit of a boy with severe factor VIII deficiency and an inhibitor. After a period of observation and conservative management, low-dose radiotherapy (750 rads) and Proplex was used. Eighteen months after radiotherapy significant healing had occurred. The role of radiotherapy in the treatment of hemophilic pseudotumor is reviewed.

Disseminated histiocytosis X complicated by diffuse erythrophagocytosis: report of two cases.

Two children with the clinical and histopathological features of disseminated histiocytosis X became refractory to chemotherapy and a diffuse erythrophagocytic process developed. No cause of the erythrophagocytosis could be found. Pancytopenia and marked erythrophagocytosis persisted until death ensued. The relationship of this disorder to familial erythrophagocytosis is discussed.

Pre-B cell cutaneous lymphoma in infancy: a unique clinical entity.

A case of a young infant with primary cutaneous lymphoma with a pre-B immunophenotype is presented. Several similar cases from the literature are summarized. Pre-B cutaneous lymphoma in young children represents a newly recognized clinical entity.

Depression in children and adolescents with malignancy.

This is a prospective and retrospective study of 35 children and adolescents with cancer treated at a pediatric Hematology-Oncology division. Using DSM-III diagnostic criteria for Major Depressive Episode, 17% of the sample were found to be depressed. This study also describes some of the distinguishing characteristics of adults and children with cancer. For example, of particularly note in this study was the apparent nonchalance of younger children diagnosed as having cancer. The children also, however, demonstrated anger more frequently, which is not a common finding in adult patients with cancer.

Osteogenic sarcoma following Hodgkin's disease.

The cases of two children who developed osteogenic sarcoma of the distal femur following prolonged remission of Hodgkin's disease are reported. These cases are unique in that the sarcoma developed in an area not previously irradiated. This occurrence suggests the possibility of genetic susceptibility to primary cancers in certain individuals, although prior chemotherapy may have contributed to this occurrence.