急性白血病患儿外周血T淋巴细胞亚群和NK细胞水平测定及临床意义

为探讨急性白血病患儿外周血T淋巴细胞亚群和NK细胞水平及意义 ,采用流式细胞技术测定 90例急性白血病患儿外周血T淋巴细胞亚群和NK细胞水平。结果 ,急性白血病患儿外周血T淋巴细胞亚群中CD3+ 、CD4+ 、CD4+ CD8+ 均明显低于对照组水平 (P <0 0 1) ,CD8+ 高于对照组水平 (P <0 0 1) ,NK细胞 (CD1 6+ 56+ )明显低于对照组水平 (P <0 0 1) ,经治疗缓解者T淋巴细胞亚群和NK细胞达正常水平。结果表明 ,T淋巴细胞亚群和NK细胞可作为急性白血病辅助诊断指标 ,为临床治疗提供实验依据     

Natural Killer Cell Activity in Children With Acute Lymphoblastic Leukemia

Thirty-four children with acute lymphoblastic leukemia (ALL) and 45 normal children as controls were tested for natural killer (NK) cell activity in vitro using the K-562 cell line as target cell. In the group of patients off all chemotherapy, the levels of NK cell activity were found to be comparable to normal controls. The levels of activity in the intermittent chemotherapy group were higher than or the same as those of normal controls. Low levels of NK cell activity were observed, shortly after intermittent chemotherapy. Patients who had more than two remissions had levels of NK cell activity comparable to normal controls. In contrast, low levels of NK cell activity were found in patients shortly before relapse, but returned to normal levels after achieving complete remission. Significant differences in the clinical stages between relapse and remission were found by paired t-test analysis (0.02 < p < 0.05).     

Transient myeloproliferative disorder in chromosomally normal newborn infant

Transient myeloproliferative disorder is a condition clinically resembling congenital acute myelogenous leukemia. As in acute leukemias the blast cell population in this disorder may have either normal or abnormal chromosomal complement. Transient myeloproliferative disorder is well recognized in neonates with a complete or mosaic trisomy 21 (Down's syndrome). We report a phenotypically and cytogenetically normal infant with this syndrome in whom only blast cells showed trisomy 21. We postulate that the pathogenesis of the transient myeloproliferative disorder in both Down's syndrome infants and those with a normal chromosomal complement is related to abnormal prenatal production of placental regulatory hemopoietic factors caused by chromosomal defect(s) confined to placental tissues.     

Transient myeloproliferation and acute myeloid leukemia in infants with Down's syndrome

Transient neonatal myeloproliferative disorders (TMD's) indistinguishable from acute leukaemia by clinical and morphological criteria have been described in neonates with Down's syndrome. To analyse its clinical significance, 10 infants under 1 year of age presenting with Down's syndrome and the morphological picture of acute myelogenous leukaemia were reviewed. 3 of these children had true AML leading to death after 2, 8 and 11 months. In the other 7 children the diagnosis TMD was suggested as spontaneous or in one case interferon-induced remission occurred within 4 to 25 weeks after diagnosis. The interferon-treated patient died of SIDS at the age of 11 months. Another one of the TMD children developed fatal erythroleukaemia at the age of 2 years. Regarding initial clinical and haematological parameters, TMD was indistinguishable from true congenital leukaemie. In all patients classification according to the FAB criteria was difficult, as mainly undifferentiated or poorly differentiated myeloid blasts were seen, sometimes with erythro- or megakaryocytic features. Because of the difficulties in the differential diagnosis of TMD and true AML it is recommended to delay specific cytostatic therapy in neonates with Down's syndrome, until definite progression of the leukaemic process is observed or cytogenetic analyses suggesting true AML are available.     

A recycling defect as a characteristic of natural killer cells in childhood acute lymphoblastic leukemia

The cytolytic function of natural killer (NK) cells and their responsiveness to interferon-alpha and IL-2 were investigated in children with acute lymphoblastic leukemia (ALL) using 51Cr-release and single-cell assays. For comparison, such NK cell functions were similarly assayed in neuroblastoma. NK activity in ALL children was extremely low at onset, but it increased gradually during remission and finally reached normal levels. At the single-cell level, their NK cells at onset were defective in the binding, lytic, and recycling abilities. Although the binding and lytic defects improved to normal levels during remission, the recycling, which increased gradually during remission, was still low even after the long-term remission in ALL: the maximal recycling capacity values were 1.9 +/- 0.4 (p less than 0.001) at onset and 4.6 +/- 0.6 (p less than 0.05) after 5 y of complete remission, as compared to the value in control children of 5.4 +/- 0.7. On the other hand, children with neuroblastoma had no recycling defect after completing the therapy: their maximal recycling capacity value was 5.6 +/- 0.7. Bone marrow cells in ALL were also depressed in their recycling ability at all stages. Interferon-alpha and IL-2 could enhance NK activity and IL-2 could generate lymphokine-activated killer activity at all stages of ALL; however, the recycling defect hardly improved with these treatments. Thus, NK cells in childhood ALL have a recycling defect as a functional characteristic.     

Natural killer cell immunodeficiency in siblings: defective killing in the absence of natural killer cytotoxic factor activity in natural killer and lymphokine-activated killer cytotoxicities

A immunodeficiency of natural killer cells as effectors for natural killer and lymphokine-activated killer cytotoxicities was first demonstrated in siblings. Two of three male siblings persistently lacked natural killer activity against K562 target cells as assayed by a 51Cr-release assay: percent lysis values were less than 1.0% as compared to the normal lymphocyte values of 43.5% +/- 6.2% (mean +/- SD). Their lymphocytes did not develop natural killer cell activity by changing effector to target ratios, prolonging the incubation time, or stimulating them with interferon-alpha or interleukin 2. Numbers of lymphocytes bearing Leu-7, CD16, or NKH-1 were normal but those of Leu-7-, CD16+ cells were decreased as estimated by flow cytometry. Single cell-in-agarose assays showed normal numbers of natural killer cells capable of binding to a target cell but incapable of killing it. They had depressed levels of lymphokine-activated killer activity, which was totally eliminated by the treatment with OKT3 and complement. This result indicates that the patients' natural killer cells are also defective in the capacity to work as effectors for lymphokine-activated killer activity. The patients' natural killer cells did not produce natural killer cytotoxic factor activity. Antibody-dependent cellular cytotoxicity and cytotoxic T lymphocyte cytotoxicity were normal. These results demonstrate a selective natural killer cell deficiency as effectors for natural killer and lymphokine-activated killer cytotoxicities with a familial tendency, in which there is defective killing with the absence of natural killer cytotoxic factor activity.     

Natural killer cell activity of peripheral blood and bone marrow mononuclear cells from patients with childhood acute lymphoblastic leukemia

Patients with untreated acute lymphoblastic leukemia had highly significantly reduced natural killer cell activity in peripheral blood (p less than 0.01) and bone marrow (p less than 0.001) mononuclear cells compared with that in peripheral blood mononuclear cells in normal healthy controls. Patients in remission had normal killer cell activity (p greater than 0.5) both in peripheral blood and bone marrow mononuclear cells. Thus, the natural killer cell activity correlated well with the disease activity in the patients.     

Natural Killer Cell Activity of Peripheral Blood and Bone Marrow Mononuclear Cells from Patients with Childhood Acute Lymphoblastic Leukemia

ABSTRACT. Patients with untreated acute lymphoblastic leukemia had highly significantly reduced natural killer cell activity in peripheral blood ( p <0.01) and bone marrow ( p <0.001) mononuclear cells compared with that in peripheral blood mononuclear cells in normal healthy controls. Patients in remission had normal killer cell activity ( p >0.5) both in peripheral blood and bone marrow mononuclear cells. Thus, the natural killer cell activity correlated well with the disease activity in the patients.     

Serum lysozyme activity in children with acute leukemia

Serum lysozyme activity was measured in samples from children with acute leukemia, malignant tumours, and in normal children. All children with acute lymphatic leukemia (ALL) had significantly reduced levels of lysozyme at diagnosis, and none of the children fell within the normal range. Children with ALL in complete remission had lysozyme levels comparable to normal children, while children with ALL in relapse also had pathological low levels. Children with ALL in remission and off therapy also had normal levels of lysozyme. Children with acute myelogenous leukemia had normal lysozyme levels, while children with monomyelocytic leukemia had substantially elevated lysozyme levels before treatment. Determination of serum lysozyme activity in children with acute leukemia is of value both for diagnosis and for evaluating the effect of therapy.     

The prognostic value of serum lysozyme activity in acute myelogenous leukemia

Serum lysozyme activity was measured in samples from adult patients with acute leukemia, malignant tumors, and in normal adults. Twenty-eight adult patients with acute myelogenous leukemia (AML) had significantly elevated levels of lysozyme at diagnosis, and none of the adults fell within the normal range. Thirty-two patients with AML in complete remission had lysozyme levels comparable to normal adults, whereas patients with AML in relapse (eight cases) also had abnormally high levels of lysozyme activity. Ten patients with AML in remission and off therapy also had normal lysozyme levels. Three patients with acute lymphatic leukemia had normal lysozyme levels, while one child with monomyelocytic leukemia had substantially elevated lysozyme levels before treatment. It seems that in patients in remission and with normal blood values, the serum lysozyme activity is valuable for monitoring the remission.     

The prognostic value of serum lysozyme activity in acute myelogenous leukemia.

Serum lysozyme activity was measured in samples from adult patients with acute leukemia, malignant tumors, and in normal adults. Twenty-eight adult patients with acute myelogenous leukemia (AML) had significantly elevated levels of lysozyme at diagnosis, and none of the adults fell within the normal range. Thirty-two patients with AML in complete remission had lysozyme levels comparable to normal adults, whereas patients with AML in relapse (eight cases) also had abnormally high levels of lysozyme activity. Ten patients with AML in remission and off therapy also had normal lysozyme levels. Three patients with acute lymphatic leukemia had normal lysozyme levels, while one child with monomyelocytic leukemia had substantially elevated lysozyme levels before treatment. It seems that in patients in remission and with normal blood values, the serum lysozyme activity is valuable for monitoring the remission.     

Megakaryoblastic Leukemia and Down's Syndrome: A Review

Megakaryoblastic leukemia and transient leukemia in Down's syndrome have been reviewed using case reports from the literature and our own experience at the Hospital for Sick Children. The following conclusions have been reached: (1) approximately 20% of leukemia (excluding transient leukemia) in Down's syndrome is acute megakaryoblastic leukemia; (2) approximately 20% of all leukemia in Down's syndrome is transient leukemia; (3) transient leukemia in Down's syndrome is acute megakaryoblastic leukemia; (4) recurrence of acute megakaryoblastic leukemia occurs in 20% of the cases of transient leukemia; and (5) the incidence of acute megakaryoblastic leukemia in Down's syndrome is estimated to be 400 times that in normal children. These observations suggest that a specific form of leukemia, namely acute megakaryoblastic leukemia, has a remarkable association with Down's syndrome.     

Serum lysozyme level in children with acute leukemia and malignant diseases

Serum lysozyme activity was measured in samples from 65 children with acute lymphatic and myelogenous leukemia, solid tumors and malignant lymphoma in comparison with 45 healthy children. All children with acute lymphatic leukemia (ALL) had significantly reduced levels of lysozyme before starting therapy compared with a control group (p less than 0,01). Children with ALL in complete remission had lysozyme levels comparable to normal children, while children with ALL in relapse showed pathological low levels again. Children with acute myelogenous leukemia (AML), solid tumors and malignant lymphomas had higher lysozyme concentration before therapy than healthy children. Determination of lysozyme activity in children with acute leukemia and malignant tumors is of value for diagnosis and to control the effect of therapy.     

Chronic natural killer cell lymphocytosis is associated with elevated cytotoxic activity of natural killer cells

The authors describe a 16-year-old girl who has suffered from chronic natural killer cell lymphocytosis (CNKL) for 12 years. From age 4 years, she has shown a persistent lymphadenopathy and lymphocytosis. Clinically, she developed allergic skin involvement, thrombocytopenia, and peripheral polyneuropathy. Annual flow cytometry analyses of lymphocyte subsets revealed persistently elevated NK cell levels (55-75% of the lymphocyte fraction and 0.7-10 x 10(3) NK cells per microliter of blood). Furthermore, IgE serum concentrations were markedly increased. Based on CD16, CD161, and CD94 surface antigen expression, the NK cell population was characterized as mature NK cells. Functional analysis of these cells showed a 2-fold increase of intrinsic cytotoxic activity toward K-562 cells compared with NK cells from healthy controls. The authors present a clinical case of rare CNKL. The patient's NK cells possess significantly increased cytotoxic activity. These findings are discussed in context with elevated IgE concentrations.     

Congenital leukemoid reaction followed by fatal leukemia. A case with Down's syndrome

A serial clinical, hematologic, and cytogenetic study was done on a baby with Down's syndrome in whom a myeloid leukemoid reaction developed at birth that spontaneously regressed within a month only to relapse two years later to an acute undifferentiated stem cell leukemia. He died 1 1/2 months after onset. The unresolved controversy of the diagnosis of the congenital leukemia-like state is discussed. The importance of following up such patients with apparent remission of their congenital leukemia-like disorder is emphasized.     

Development of natural killer cytotoxicity during childhood: marked increases in number of natural killer cells with adequate cytotoxic abilities during infancy to early childhood.

The cytotoxicity of natural killer (NK) cells against K562 cells and their responsiveness to interferon-alpha and interleukin 2 (IL-2) were studied throughout childhood using 51Cr-release and single-cell assays. Although NK activity was extremely low in the neonatal period, it almost reached the adult level during 1 to 5 mo of age and remained at that level thereafter. At the single-cell level, the binding, lytic, and recycling abilities were also depressed in the neonatal period, but these abilities improved conspicuously after this period; in particular, the lysis and recycling were at higher levels during 6 mo to 4 y of age. The absolute numbers of circulating cytotoxic NK cells were high during infancy to early childhood: they were 54 +/- 24 (mean +/- SD/mm3) in neonates, 115 +/- 48 in 1- to 5-mo-old infants, 121 +/- 42 in 6- to 12-mo-old infants, 93 +/- 26 in 1- to 4-y-old children, and 42 +/- 16 in adults. Interferon-alpha and IL-2 could enhance NK activity throughout childhood. The IL-2 enhancement was prominent especially in the neonatal period; IL-2 yielded a 2.5-fold increase in the number of cytotoxic cells and improved the recycling to the adult level. At older ages, interferon-alpha and IL-2 yielded 1.4- and 1.9-fold increases in the number of cytotoxic cells, respectively, but did not enhance the recycling. The increased number of NK cells with adequate cytotoxic abilities during infancy to early childhood indicates the predominance of NK immunity during these periods. IL-2 is a cytokine that induces high levels of NK cytotoxicity even in neonates.     

survivin在儿童急性白血病细胞中的定位表达及与化疗的关系

目的：探讨survivin在急性白血病中的表达、细胞中的定位及与临床疗效的关系,并从细胞水平说明survivin定位表达与化疗疗效的关系。方法：应用免疫组织化学链霉亲和素、生物素、过氧化物酶复合物方法,检测62例急性白血病患儿和40例同期住院患儿(排除急性白血病)骨髓细胞survivin的表达,survivin在细胞中的定位。同时用SABC法检测不同浓度柔红霉素作用的Molt-4细胞中survivin定位表达的变化,用流式细胞术检测细胞凋亡率。结果：在62例急性白血病患儿中,survivin蛋白表达阳性率为41.9%(26/62),明显高于非急性白血病骨髓5.0%(2/40)(χ2=16.66,P<0.01);survivin在胞浆中的表达为46.2%(12/26),在胞核中的表达为53.9%(14/26),差异无统计学意义(χ2=0.3077,P>0.05),但二者第19天缓解率差异有显著性(P<0.05),sur-vivin胞核表达阳性者缓解率高于胞浆阳性表达者。DNR处理的Molt-4细胞survivin表达降低,呈时间和剂量依赖性,而且survivin从胞浆移位到胞核,流式细胞术显示细胞凋亡率也呈剂量和时间依赖性。结论：①survivin在儿童急性白血病中表达率为41.9%,提示其在儿童急性白血病发生、发展和预后中的意义;②survivin在胞浆和胞核的不同表达与临床化疗疗效有关,可作为判断预后的指标;③DNR可以降低白血病细胞中survivin表达,并使其从胞浆移位到胞核,诱导细胞凋亡。     

Transient myeloproliferative disorder in Down's syndrome: three cases with megakaryocytic markers.

In this paper we describe three infants with Down's syndrome and transient myeloproliferative disorder. The blast cells of all three displayed positive megakaryocytic markers. One patient developed acute megakaryoblastic leukemia in his second year, with blasts identical to those of the initial episode. The other two cases remain well at 12 and 15 months of age.     

Isolated trisomy 21 in blasts of an acute lymphoblastic leukemia

A two years and four months old boy without evidence of Down's syndrome exhibited a trisomy 21 in his acute lymphoblastic leucemic cells. During remission this chromosomal change disappeared. The cytogenetic examination of malignant cells serves an important tool in diagnosis and follow-up of acute leucemia as well as bone marrow transplantation.