Initial changes of rat leukemia induced by 1-ethyl-1-nitrosourea and 1-butyl-1-nitrosourea.

The initial histological changes of leukemia were investigated in rats to which 1-ethyl-1-nitrosourea and 1-butyl-1-nitrosourea were orally administered. The appearance of orthochromatic erythroblasts in the peripheral blood was used as the index of the initial stage of leukemia. The rat leukemia progressed from solitary lesions to scattered and further diffuse lesions. These leukemias are thought to begin as one, or only a few nodular foci, mainly in the bone marrow and partly in the spleen.     

Erythroblasts as an index of initial stage of 2,7-FAA,ENU and BNu-induced rat leukemia

The appearance of orthochromatic erythroblasts in the peripheral blood was evaluated as an index of the initial stage of leukemia induced in rats by the oral administration of N,N'-2,7-fluorenylenebisacetamide, 1-ethyl-1-nitrosourea and 1-butyl-1-nitrosourea. Solitary leukemia lesions found mainly in the bone marrow and composed of one or a few nodular foci were found by using erythroblasts as an index. The time interval from the first appearance of erythroblasts to autopsy was short in solitary lesions, slightly longer in scattered lesions, and even longer in diffuse leukemia lesions. Although the appearance of orthochromatic erythroblasts in the peripheral blood was due to several causes other than leukemia, this appearance was useful as an index of the initial stage of chemically induced leukemia in rats.     

CLASSIFICATION OF INITIAL LEUKEMIC CHANGES IN RATS FED N,N'-2,7-FLUORENYLENEBISACETAMIDE

Leukemia was Induced in rats which were fed N,N'-2,7-fluorenyIene-bisacetamide. This leukemia developed from a solitary lesion to a scattered and further a diffuse lesion. The appearance of orthochromatic erythroblasts In the peripheral blood was utilized for detection of solitary lesions. Almost all bones of the body were examined histologically. The classification of leukemia was performed from diffuse lesions toward scattered and solitary lesions. Solitary lesions were classsifled into mature granulocytic, erythroblastic, mlcromyeloblastic, and unclassified types. No solitary lesion of myeloblasts type was identified. Each type showed its particular histological pattern from the initial stage, though solitary lesions were composed of more Immature cells than those of scattered and diffuse lesions. Mature granulocytic and erythroblastic leukemias are considered to begin as one or a few nodular foci mainly in the bone marrow. Micromyeloblastic leukemia seems to originate in the spleen and bone marrow.     

SHP-1和JAK1基因在初治急性白血病患者中的表达

目的：探讨SHP-1和JAK1基因在初治急性白血病（AL）细胞的转录表达及其与初治AL患者化疗效果的关系。方法：采用半定量逆转录-聚合酶链反应（RT-PCR）方法检测60例初治AL患者骨髓单个核细胞及20例健康人外周血单个核细胞中SHP-1和JAK1 mRNA的表达。结果：60例初治AL患者SHP-1和JAK1的mRNA表达阳性率分别为30%，100%；初治AL患者SHP-1 mRNA表达水平明显低于正常对照组（P<0.001），JAK1 mRNA表达水平较正常对照组略增高，但差异无统计学意义（P=0.180）,初治AL患者SHP-1 mRNA阳性组的诱导化疗完全缓解（CR）率为88.9%，阴性患者组CR率为54.8%，差异有统计学意义（P=0.005）。SHP-1与JAK1 mRNA表达呈负相关（P=0.046）。结论：SHP-1可能是白血病潜在的抑制基因，可望作为判断初治急性白血病患者疗效和预后的指标。     

Early metastatic stage of 2,7-FAA-induced leukemia in rats

The development from primary focus to metastasis was histologically investigated in 2,7-FAA-induced leukemia in rats. The Wistar and Sprague-Dawley strains were used, and the results were similar in both strains. The spread of lesions was classified as solitary, scattered or diffuse. Scattered leukemia lesions were divided into two groups: A and B: (A) consisted of one or a few conspicuously large foci and many small foci, and (B) had no such large foci. The interval from the first appearance of orthochromatic erythroblasts to autopsy was short in animals with solitary lesions, slightly longer in those with scattered lesions in group (A), and still longer in group (B). Conspicuously large foci were predominantly localized in the bone marrow, while small foci were scattered in the bone marrow, spleen and liver. The (A) scattered lesions were considered to represent the early metastatic stage, since they consisted of the combination of large and small foci, and the time interval from the first appearance of erythroblasts to autopsy was between that of solitary lesions and (B) scattered lesions. The leukemia induced in rats by 2,7-FAA occurred predominantly in the bone marrow, which was the primary site. It was thought that this leukemia spread rapidly to other regions of the bone marrow, and to the spleen and liver, by hematogenous metastasis.     

Nonhealing ulcer--a rare initial presentation of chronic myeloid leukemia diagnosed on aspiration cytology

Involvement of skin in hematologic malignancies is rare phenomena as majority of the dermatologic lesions in leukemia patients are nonleukemic. In the absence of preceding history of leukemia, the diagnosis is often a surprise. Chronic nonhealing ulcer on the back of a 65-years-old male prompted a fine needle aspiration from its base. Smears showed an unexpected picture comprising of leukocytes in various stages of maturation against a hemorrhagic background. A cytologic diagnosis of leukemia cutis was given. Subsequent hematologic investigations revealed chronic myeloid leukemia in chronic phase. Cutaneous involvement is a rare initial presentation of leukemia in an otherwise asymptomatic patient and also an uncommon cause of nonhealing ulcer. Aspiration cytology scores over biopsy in not only being a rapid and easy diagnostic tool but also allows better appreciation of cellular details like cytoplasmic granules.     

流式细胞仪检测急性婴幼儿白血病干细胞

背景：有关儿童急性髓细胞性白血病干细胞含量的测定及急性髓细胞性白血病患儿缓解后白血病干细胞含量与急性白血病微小残留病之间关系的研究国内外未见报道。 目的：通过测定急性髓细胞性白血病干细胞或急性髓细胞性白血病干细胞-IPIC在儿童急性白血病患儿骨髓单个核细胞中的含量,研究急性髓细胞性白血病患儿缓解后白血病干细胞含量与急性白血病微小残留病水平之间的关联。 方法：收集白血病患儿113例次。采用骨髓单个核细胞分离及单细胞悬液制成单细胞悬液,进行单个核细胞染色、急性髓细胞性白血病干细胞分析及根据初诊免疫表型获得白血病相关表型,并采用该白血病相关免疫表型进行单抗组合和流式细胞术测定分析。 结果与结论：①初诊急性髓细胞性白血病组骨髓单个核细胞中急性髓细胞性白血病干细胞含量明显高于初诊急性淋巴细胞性白血病组和非肿瘤对照组(P均< 0.017),初诊急性淋巴细胞性白血病组骨髓单个核细胞中急性髓细胞性白血病干细胞-IPIC含量显著高于非肿瘤对照组(P < 0.017)。②对33例次缓解急性髓细胞性白血病患儿急性髓细胞性白血病干细胞和急性白血病微小残留病相关性分析发现,两者存在显著负相关性。结果提示,①急性髓细胞性白血病干细胞-IPIC也存在于初诊急性淋巴细胞性白血病患儿骨髓细胞中,且当急性淋巴细胞性白血病获完全缓解时急性髓细胞性白血病干细胞-IPIC含量却没有下降,但非肿瘤对照组标本中急性髓细胞性白血病干细胞-IPIC的含量极微。②急性髓细胞性白血病患儿缓解后骨髓中急性髓细胞性白血病干细胞含量和急性白血病微小残留病水平之间存在着明显的负相关。     

白血病细胞TGF-β1含量减少及外源性TGF-β1基因对HL-60细胞的作用

目的：研究白血病细胞是否存在转化生长因子β1（TGF-β1）量的异常以及这种异常在白血病发病机制中的可能作用。 方法： 应用ELISA法检测白血病细胞株和原代白血病细胞培养上清TGF-β1水平，进一步应用脂质体介导基因转移法将TGF-β1基因转染HL-60细胞，采用有限稀释法及G418筛选得到抗性细胞，应用RT-PCR、白血病细胞集落培养、裸鼠移植瘤成瘤试验、片段化DNA分析、流式细胞术检测HL-60细胞内TGF-β1、bcl-2、端粒酶反转录酶（hTERT）mRNA的表达变化等方法了解外源性TGF-β1基因对HL-60细胞体内外增殖、凋亡的影响。 结果： 白血病细胞株和原代白血病细胞培养上清TGF-β1水平明显低于正常对照组(P<0.01)，转染TGF-β1基因后，HL-60细胞内TGF-β1 mRNA表达上调，bcl-2、hTERT mRNA表达下调，细胞体外增殖受抑制，集落形成抑制率达78.3%，裸鼠移植瘤生长受抑制，荷瘤鼠生存期延长，细胞呈现凋亡特征性的梯形条带，凋亡比例达73.4%。 结论： 内源性TGF-β1水平降低是白血病的发病机制之一,外源性TGF-β1基因能够抑制HL-60细胞增殖，诱导细胞凋亡,该基因通过下调bcl-2、hTERT mRNA的表达而发挥作用。     

Febrile neutrophilic dermatosis associated with acute leukemia

Febrile neutrophilic dermatosis (Sweet's Syndrome) is an uncommon syndrome characterized clinically by fever, neutrophilia, and erythematous, non-ulcerating papules or plaques on the face, neck, upper thorax, and extremities. A case associated with acute myelogenous leukemia is reported and nine other reported cases associated with acute non-lymphocytic leukemia are reviewed. The appearance and location of the lesions on the face, neck, upper trunk and extremities, a female predominance, an associated fever, marked dermal infiltrates of mature neutrophils, and rapid clearing of lesions with parenteral corticosteroids were manifestations similar to febrile neutrophilic dermatosis not associated with leukemia. Although the etiology of febrile neutrophilic dermatosis associated with acute leukemia is unknown, the resolution of lesions and symptoms with systemic corticosteroids and recurrence with relapse of leukemia suggests an immune process with the leukemic cell population serving as a possible antigenic source.     

Translocation between chromosomes 1 and 9 in childhood acute lymphoblastic leukemia

A case of a non-T, non-B acute lymphoblastic leukemia with a translocation between chromosomes #1 and #9 is described. The breakpoints in these chromosomes were determined to be at bands 1q23 and 9p22, respectively. The breakpoint in chromosome #1 was at the same site as that in a subgroup of acute lymphoblastic leukemia with t(1;19), and the breakpoint in #9 was the same as that in t(9;11)(p22;q23) in acute monoblastic leukemia. We discuss the possible association between these chromosome bands (1q23, 9p22, 11q23, and 19p13) and the morphologic features of the leukemic cells. The breakpoint in chromosome band 1q23 may be specifically associated with acute lymphoblastic leukemia.     

Pituitary tumors in patients with MEN1 syndrome

We briefly review the characteristics of pituitary tumors associated with multiple endocrine neoplasia type 1. Multiple endocrine neoplasia type 1 is an autosomal-dominant disorder most commonly characterized by tumors of the pituitary, parathyroid, endocrine-gastrointestinal tract, and pancreas. A MEDLINE search for all available publications regarding multiple endocrine neoplasia type 1 and pituitary adenomas was undertaken. The prevalence of pituitary tumors in multiple endocrine neoplasia type 1 may vary from 10% to 60% depending on the studied series, and such tumors may occur as the first clinical manifestation of multiple endocrine neoplasia type 1 in 25% of sporadic and 10% of familial cases. Patients were younger and the time between initial and subsequent multiple endocrine neoplasia type 1 endocrine lesions was significantly longer when pituitary disease was the initial manifestation of multiple endocrine neoplasia type 1. Tumors were larger and more invasive and clinical manifestations related to the size of the pituitary adenoma were significantly more frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Normalization of pituitary hypersecretion was much less frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Pituitary tumors in patients with multiple endocrine neoplasia type 1 syndrome tend to be larger, invasive and more symptomatic, and they tend to occur in younger patients when they are the initial presentation of multiple endocrine neoplasia type 1.     

急性髓系白血病细胞血管细胞黏附分子1、CD34和CD117的表达

背景：血管细胞黏附分子1与白血病浸润密切相关,白血病细胞本身是否表达血管细胞黏附分子1,以及与疾病难治是否相关尚无定论。 目的：分析血管细胞黏附分子1、CD34、CD117在急性髓系白血病细胞表面的表达,3者之间的相互关系及与难治性急性髓系白血病的相关性。 方法：采用流式细胞技术检测16例急性髓系白血病细胞中血管细胞黏附分子1、CD34、CD117的表达,其中难治组6例,非难治组10例;同时以正常骨髓单个核细胞标本作对照。 结果与结论：急性髓系白血病细胞CD34、CD117表达高于对照组(P < 0.05)。难治组急性髓系白血病细胞CD34表达明显高于非难治组(P < 0.05)。难治组与非难治组CD117表达差异无显著性意义(P > 0.05)。急性髓系白血病细胞血管细胞黏附分子1表达与对照组比较差异无显著性意义(P > 0.05)。难治组与非难治组血管细胞黏附分子1表达差异无显著性意义(P > 0.05)。表明急性髓系白血病细胞伴CD34表达,为不良预后指标之一,CD117、血管细胞黏附分子1表达与其是否难治无明显相关性。     

Expression of TCL1 in hematologic disorders.

OBJECTIVE: TCL1, MTCP1 and TCL1b are three members of a new family of oncogenes that are expressed in T cell leukemias of ataxia telangiectasia patients (T-PLL, T-CLL). TCL1 is located at 14q32.1 and activated by juxtaposition to the alpha/delta-locus at 14q11 or beta-locus at 7q35 of the T cell receptor during the reciprocal translocations t(14;14)(q11;q32), t(7;14)(q35;q32), or inversion inv(14)(q11;q32). TCL1 encodes a predominantly cytoplasmic protein of 114 aa (14 kD) of unknown function. Recent studies suggest that TCL1 promotes cell survival rather than stimulating cell proliferation, as previously proposed. METHODS: In an attempt to clarify the contexts in which TCL1 is expressed, we investigated TCL1 expression in 114 lymphoma and leukemia patients by Northern blot, RT-PCR and immunohistochemistry. RESULTS: TCL1 expression is restricted to lymphoid cells, and is found in neoplastic (T and B cell neoplasms, and Hodgkin's disease) and nonneoplastic proliferations (reactive lesions). Out of 114 cases, 18 neoplasms of myeloid and 4 cases of epithelial origin were TCL1-negative. In lesions of the lymphoid system, both low- and high-grade lymphomas were found to express TCL1. CONCLUSIONS: We propose that TCL1 expression especially in high-grade B cell non-Hodgkin's lymphomas might interfere with B cell differentiation and promote the transition from low- to high-grade lymphoma.     

Hepatotoxicity of (chloro-2-ethyl)-1-cyclohexyl-3-nitroso-1-urea (CCNU) in the rat

Few cases of liver involvement have been reported in patients receiving treatment with CCNU. CCNU is an anti-tumoral agent used in the treatment of leukemia, Hodgkin's disease and bronchial or cerebral tumors. A single daily dose of 20 or 50 mg/kg CCNU in female Wistar rats induces an important increase of transaminases, reaching 10 times initial level between day 2 and day 6, followed by a second and moderate increase between day 21 and day 28. Three-fold increased alkaline phosphatases and conjugated hyperbilirubinemia were noted for the two doses, and was greater for the higher dose. Histological and ultrastructural studies showed two types of lesions: during the first phase of transaminase elevation, edema and inflammatory infiltration of the portal spaces; during the second phase of transaminases elevation, numerous bundles of pericanalicular microfilaments and severe dilation of the biliary tract. Hepatic cells had few alterations although some necrotic foci were observed, particularly at the higher dose. So CCNU induced an intrahepatic cholestasis with pericholangitis in the rat.     

Site of origin of 2,7-FAA-induced rat leukemia.

Oral administration of N,N'-2,7-fluorenylenebis-acetamide (2,7-FAA) induces mature granulocytic and erythroblastic leukemia in rats. We compared the primary site of mature granulocytic leukemia with that of erythroblastic leukemia. The nodular foci of solitary lesions and comspicuously large foci of scattered lesions were considered to be the primary site. They appeared mainly in the bone marrow of various bones. The primary site of mature granulocytic leukemia appeared more frequently in short bones than in long bones. On the contrary, that of erythroblastic leukemia appeared more frequently in long bones than in short bones. The origin of mature granulocytic leukemia seems to be concerned with bone tissue, while erythroblastic leukemia may have little relation with bone tissue.     

SITE OF ORIGIN OF 2,7-FAA-INDUCED RAT LEUKEMIA

Oral administration of N,N'-2,7-fluorenylenebis-acetamide (2,7-PAA) induces mature granulocytic and erythroblastic leukemia in rats. We compared the primary site of mature granulocytic leukemia with that of erythroblastic leukemia. The nodular foci of solitary lesions and conspicuously large foci of scattered lesions were considered to be the primary site. They appeared mainly in the bone marrow of various bones. The primary site of mature granulocytic leukemia appeared more frequently in short bones than in long bones. On the contrary, that of erythroblastic leukemia appeared more frequently in long bones than in short bones. The origin of mature granulocytic leukemia seems to be concerned with bone tissue, while erythroblastic leukemia may have little relation with bone tissue.     

WT1基因异构体的转导及永久表达白血病细胞株的建立

目的：将携带WT1基因的4种异构体全长cDNA真核表达载体转导白血病细胞株NB4，为进一步研究WT1基因及其异构体对白血病细胞生物学功能的影响奠定实验基础。 方法： 用电穿孔的方法将携带WT1基因四种异构体全长cDNA的真核表达载体转染白血病细胞株NB4，通过药物筛选获得永久表达细胞株，并将此基因修饰细胞进行单克隆化，通过基因组DNA PCR，RT-PCR及Western印迹法证实外源基因在NB4细胞中的稳定整合及表达。 结果： WT1基因异构体成功转染白血病细胞株NB4，外源基因在NB4细胞中的稳定整合及表达。 结论： WT1基因异构体能够通过电穿孔的方法转染白血病细胞并建立永久表达细胞株。     

Skeletal clues apparently distinguishing Waldenstrom's macroglobulinemia from multiple myeloma and leukemia

This study was conducted to characterize macroscopically and by conventional radiography the bony lesions in a case of Waldenstrom's macroglobulinemia and to compare and contrast it with those of the other major hematologic lymphoproliferative disorders, multiple myeloma and leukemia. Two varieties of lytic skeletal lesions were found in Waldenstrom's macroglobulinemia. One was sharply defined, spheroid lesions with smooth borders and effaced/erased trabeculae. The second was in the form of coalescing pits (holes) with smooth, minimally remodeled edges. The appearance combined features of multiple myeloma and leukemia, but were mutually exclusive in those diseases. Spheroid lesions with effaced edges were absent in leukemia, while pits were absent in multiple myeloma. Fronts of resorption were not noted in Waldenstrom's macroglobulinemia. The combination of some of the features of leukemia and myeloma appear to allow recognition of Waldenstrom's macroglobulinemia. Am. J. Hum. Biol. 14:532–537, 2002. © 2002 Wiley‐Liss, Inc.