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PubMed2002

Human T-cell leukemia virus type I Tax transactivates the matrix metalloproteinase-9 gene: potential role in mediating adult T-cell leukemia invasiveness.

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia (ATL) and of tropical spastic paraparesis/HTLV-I-associated myelopathy. Infiltration of various tissues by circulating leukemic cells is a characteristic of ATL. Matrix metalloproteinases (MMPs), which mediate the degradation of the basement membrane and extracellular matrix, play an important role in metastasis and tumor cell dissemination. The aim of this study was to explore whether expression of MMP-2 and MMP-9 was deregulated by HTLV-I infection. The data showed that HTLV-I-infected T-cell lines expressed high levels of MMP-9 compared with uninfected T-cell lines. In contrast, the levels of the related MMP-2 were not significantly altered by HTLV-I infection. In addition, the elevated expression of MMP-9 in HTLV-I-infected cells was attributable to the action of the viral transactivator protein Tax. The results show that Tax can activate the MMP-9 promoter and induce MMP-9 expression in T cells, indicating that the constitutive expression of MMP-9 in virus-infected cell lines is at least in part mediated by Tax. Activation of the MMP-9 promoter by Tax occurs mainly through the action of NF-kappaB and SP-1. The biologic significance of these observations was validated by the following 2 findings: MMP-9 expression was increased in primary ATL cells, and plasma MMP-9 levels were elevated in ATL patients. In addition, plasma levels of MMP-9 correlated with organ involvement in ATL patients. Together these data suggest that overexpression of MMP-9 in HTLV-I- infected cells may be in part responsible for the invasiveness of ATL cells.

Enzyme Induction↗
PubMed1992

Reactivity profiles of leukemic myeloblasts with monoclonal antibodies directed to sialosyl-Le(x) and other lacto-series type 2 chain antigens:absence of reactivity with normal hematopoietic progenitor cells.

We investigated the expression profiles of lacto-series type 2 antigens in hematopoietic cells and their progenitors, in comparison with leukemic leukocytes. Reactivity profiles of various anti-type 2 chain monoclonal antibodies (MoAbs) with leukemic blasts from 12 patients with acute myeloblastic leukemia (AML) and those from two patients with acute unclassified leukemia (AUL) show that anti-sialosyl-Le(x) MoAb SNH3 reacted strongly with greater than 95% of leukemic blast leukocyte populations from all patients (14 of 14). Another anti-sialosyl-Le(x) MoAb, FH6, showed less reactivity than SNH3 (12 of 14 patients), while anti-Le(y) MoAb AH6 showed reactivity with only 8 of 14 patients. On the other hand, none of the anti-type 2 chain MoAbs reacted with CD34+ normal adult bone marrow (BM) mononuclear cells obtained independently from three healthy volunteers. MoAb SNH3, but not FH6 or AH6, showed complement-mediated cytotoxicity to leukemic blasts from these patients, as well as to myelogenous leukemia cell line HL60. Colony-forming unit granulocyte-macrophage (CFU-GM), but not burst-forming unit-erythroid (BFU-E), was incompletely inhibited by treatment of normal BM mononuclear cells with SNH3 and complement. The absence of type 2 chain antigen expression in hematopoietic progenitor cells and in in vitro hematopoietic colonies (CFU-GM and BFU-E) strongly suggests that application of anti-carbohydrate MoAbs, particularly anti-sialosyl-Le(x) could be useful for elimination of leukemic myeloblasts infiltrating in BM, for purging of leukemic blasts in BM, and for facilitation of autologous BM transplantation.

Antibodies, Monoclonal↗
PubMed1995

A rapid fatal erythroleukemia caused by J2E cells can be treated ex vivo with erythropoietin.

The J2E cell line is an immature erythroid line which terminally differentiates in response to erythropoietin (epo), producing mature, hemoglobin-synthesizing red blood cells. We have shown that when these cells were injected into mice a rapid and fatal erythroleukemia developed with symptoms of severe anemia and hepatosplenomegaly. Southern blotting demonstrated that the leukemic cells were the introduced J2E cells. In addition to spleen and liver, the bone marrow was a major site of leukemic cell infiltration, and when grown in vitro leukemic cells from bone marrow remained responsive to erythropoietin. We reasoned, therefore, that treatment of mice with this hormone should alleviate the erythroleukemia, but regular injections of epo in vivo failed to arrest the progress of the disease. However, when bone marrow from leukemic mice was exposed continuously to the hormone ex vivo, before reinfusion into naive recipients, a marked extension in life span was observed. It was concluded that ex vivo epo treatment could be used therapeutically for J2E cell erythroleukemias.

Animals↗
PubMed1983

Malignant gingival and skin "infiltrates" in adult leukemia.

The clinicopathologic and histopathologic features of leukemic gingival and cutaneous "infiltrates" were studied in 1,076 adults hospitalized for cancer chemotherapy. Leukemic gingival hyperplasia was present in 3.6 percent and leukemia cutis in 3.1 percent of the patients. Only 7.6 percent of those with leukemic "infiltrates" had simultaneous gingival and skin involvement. Histologically, the lesions consisted of extravasated and proliferating monocytoid or myeloid cells. The infiltrative-proliferative tendency was most pronounced in patients with, in a sharply descending order, acute monocytic leukemia, acute myelomonocytic leukemia, and acute myelocytic leukemia. Formation of lesions in the skin and gingiva was unrelated to sex, age, and white blood cell count. Gingival lesions were particularly prone to infectious complications in patients with poor oral hygiene. Aside from the morphologic predisposition, the propensity for adults with leukemia to develop chemotherapeutically reversible malignant mucocutaneous lesions was highly individualistic and unpredictable.

Adolescent↗
PubMed1989

[Portal hypertension in chronic lymphocytic leukemia].

Portal hypertension in chronic lymphocytic leukemia (CLL) is rare. A 64-year-old woman with CLL for 5 years and increasing hepatosplenomegaly developed portal hypertension and bleeding gastric varices. There was no portal vein thrombus by abdominal echography and angiography. Following splenectomy and devascularization of the fornix, the gastric varices disappeared. The liver biopsy showed dense leukemic cell infiltration in portal triads, but no fibrosis. The portal hypertension in this case may be mainly due to increased portal flow from the enlarged spleen and leukemic cell infiltration in the liver. Previously reported cases are summarized.

Esophageal and Gastric Varices↗
PubMed2003

A diagnosis of chronic lymphocytic leukemia prompted by cutaneous lymphocytic infiltrates present in mohs micrographic surgery frozen sections.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States. Patients with CLL are at an increased risk for the development of second malignant neoplasms, the most common of which is cuta-neous squamous cell carcinoma (SCC). Cutaneous infiltrates of CLL have been reported in association with primary cutaneous neoplasms, including SCC, basal cell carcinoma, and actinic keratosis. The finding of a dense lymphocytic infiltrate surrounding a cutaneous neoplasm should prompt consideration of possible underlying CLL. OBJECTIVE: To review the relationship of CLL to cutaneous SCC and to raise awareness of the possible coexistence of these two neoplasms. METHODS: The case report describes a patient with a SCC of the left cheek treated with Mohs micrographic surgery. A dense lymphocytic infiltrate was noted on the frozen sections, and a complete blood count was obtained. RESULTS: A lymphocytosis was detected, leading to the diagnosis of CLL, stage 0. CONCLUSION: Patients with CLL are at an increased risk for the development of cutaneous neoplasms. An infiltrate of leukemic cells in documented CLL patients can be associated with cutaneous neoplasms such as SCC. We present a patient with no known hematologic malignancy who demonstrated a dense lymphocytic infiltrate on Mohs sections. The diagnosis of CLL was considered based on the appearance of this infiltrate. Subsequently, a new case of CLL was confirmed with appropriate testing. The finding of a dense subcutaneous infiltrate of lymphocytes on Mohs frozen sections should raise the possibility of CLL and lead to appropriate screening tests.

Aged↗
PubMed1992

[A clinicopathological study of leukemic kidney].

A clinicopathological study of leukemic kidney was carried out by observing the changes of the kidney in 104 autopsied cases of leukemia. The main changes of the leukemic kidney were increase of renal weight, calcinosis of renal tubules, interstitial leukemic cell infiltration, intravascular stasis and renal bleeding. Calcinosis intravascular stasis, renal bleeding as well as hyperuricemia may lead to abnormal urinary findings. The presence and severity of interstitial infiltration have no obvious relation with the level of blood urea nitrogen, creatinine and muric acid as well as the abnormal change of the urine. However, the presence of intravascular stasis by leukemic cells are correlated with the disturbance of renal function.

Adolescent↗
PubMed1992

[Leukemia cutis: clinical and histopathological analysis of 14 cases].

We report 14 cases of leukemia cutis registered at Department of Dermatology, Veterans General Hospital Over a period of 18 years. There were one patient with acute lymphocytic leukemia (ALL), one with chronic lymphocytic leukemia (CLL), seven with acute monocytic leukemia (AMOL), one with acute myelomonocytic leukemia (AMML), and four with chronic myelocytic leukemia (CML). Multiple papules and nodules were the most frequent clinical lesions. Metastatic skin lesions occurred most commonly on legs (71%), followed by arms (64%), back (50%), anterior chest (50%), scalp (14%), and face (14%). The feet (7%) were rarely involved while palms and soles were rarely involved. Cutaneous leukemic lesions may be concomitant with or after, but never before the diagnosis of systemic leukemia in our series has had such change. In general, the histopathology of leukemia cutis showed diffuse or nodular infiltration of leukemic cells in the dermis and subcutaneous tissue, often typing of leukemia relays on more confirmative studies of peripheral smear and bone marrow biopsy. Leukemia cutis seems to be dissemination of systemic leukemia to the skin, and the presence of cutaneous leukemic lesions are associated with a very poor prognosis. Most patients (85%) died within 4 months after appearance of skin metastasis.

Adolescent↗
PubMed2003

A case of leukemia of the appendix presenting as acute appendicitis.

A 71-year-old man was admitted to our hospital because of right lower abdominal pain. He was suspected of having acute appendicitis and soon after admission, appendectomy was performed. Macroscopically, the appendix was greatly swollen and reddened, but had no abscess. Microscopically, polymorphonuclear leukocytes were not found, but diffuse infiltration of atypical cells was observed. Examination of a bone marrow aspirate revealed 74% blasts that were peroxidase stain positive. We diagnosed acute myelogenous leukemia (FAB classification, M2). He received induction chemotherapy, but died 49 days after admission. Leukemic cell infiltration of the appendix is rare and acute appendicitis as the initial manifestation of leukemia is even rarer.

Aged↗
PubMedDate not supplied

A human acute lymphoblastic leukemia line with the T(4;11) translocation as a model of minimal residual disease in SCID mice.

This study describes a new human acute lymphoblastic leukemia (ALL) cell line (ALL-PO) with the t(4;11) translocation established in SCID mice. The ALL-PO line can be maintained by serial transplant in SCID mice with stable immunophenotypic, molecular and karyotypic features. After intravenous (i.v.) injection ALL-PO spread systemically involving the hematopoietic organs and the central nervous system (CNS) of all mice. The homing and the progression of the disease are evaluated by histological analysis and reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of the t(4;11) translocation in the bone marrow, spleen and CNS of SCID mice at different times after engraftment. Occult leukemia was detectable by PCR in the bone marrow of SCID mice as early as three days after the i.v. injection of leukemic cells whereas the first signs of involvement of the spleen and CNS appeared after 14 days; after 24 days all the mice were euthanized because they were moribund and the bone marrow, spleen and CNS showed ample infiltration by leukemic cells. The sensitivity to conventional chemotherapy was tested in this model. ALL-PO in SCID mice did not respond to treatment with vincristine or idarubicin but cyclophosphamide (150 mg kg(-1) i.v., single injection) significantly increased the survival of the mice. The efficacy of such a treatment was more evident when cyclophosphamide was given in the early stages of the disease (detectable only by molecular analysis) but much less effective when the drug was administered when the disease could be detected by conventional histological analysis. The biological behavior and molecular characteristics of ALL-PO make it a good model for studying novel therapeutic strategies for a better control of minimal residual disease.

Animals↗
PubMed1996

Identification of human juvenile chronic myelogenous leukemia stem cells capable of initiating the disease in primary and secondary SCID mice.

Most juvenile chronic myelogenous leukemia (JCML) cells have limited long-term proliferative capacity, and only a minority of immature cells give rise to colonies in semisolid cultures. Clonogenic JCML progenitors cannot be maintained in culture because they differentiate, and within a few weeks the leukemic clone is lost. This makes it difficult to identify the cell that initiates and maintains the disease in patients. To determine the proliferative capacity of JCML cells in vivo, bone marrow (BM), peripheral blood, or spleen cells from eight patients with JCML either at diagnosis or during treatment were transplanted into sublethally irradiated severe combined immune deficient (SCID) mice. JCML cells from all patients homed to the murine BM and proliferated extensively in response to exogenous stimulation with granulocyte-macrophage colony-stimulating factor. Within a few weeks, highly engrafted mice became ill and cachectic due to infiltration of leukemic cells and secretion of tumor necrosis factor-alpha. Murine BM, spleen, and liver were infiltrated with leukemic blasts, and typical JCML colony-forming progenitors could be recovered. Kinetic experiments demonstrated that only a small minority of transplanted cells homed to the murine BM, and that these cells initiated and maintained the disease in vivo by extensive proliferation and differentiation. To characterize the cell-surface phenotype of the JCML initiating cell (JCML-IC), JCML blood or spleen cells were fractionated on the basis of CD34/CD38 marker expression and transplanted into SCID mice. Only immature CD34+ cells could initiate the disease, while mature CD34- cells did not engraft. Within the CD34+ compartment, there was enrichment for JCML-ICs by immature cells with a CD34+/CD38- stem-cell-like phenotype. Mice transplanted with more mature CD34+/CD38+ populations that also contained clonogenic JCML progenitors were poorly engrafted. These results indicate that the JCML-IC is an earlier stage of development than clonogenic JCML progenitors. Additional evidence that the JCML-IC has stem-cell properties comes from secondary transplant experiments that test the self-renewal capacity. The JCML-IC from all three patients tested could successfully reinitiate the disease in secondary murine recipients. Thus, we have developed a functional in vivo model that replicates many aspects of human JCML, and have used this model to identify and characterize JCML-ICs and their stem-cell properties.

Animals↗
PubMed1983

[Case of disseminated necrotizing leukoencephalopathy following intrathecal methotrexate in acute lymphocytic leukemia].

Disseminated necrotizing leukoencephalopathy was found upon autopsy of a 32-year-old man with acute lymphocytic leukemia. He had been treated with intrathecal methotrexate for CNS involvement; no radiation therapy had been given. Autopsy findings revealed that in the white matter of the temporal lobe, there was widespread necrosis associated with numerous foam cells, demyelination, vacuolization and slight gliosis; in this lesion, leukemic cells infiltrated the Virchow-Robin space. In the white matter of other lesions we found discrete multifocal necroses of coagulative type associated with round or rod-shaped axonal swelling partly accompanied with calcification. However, in these lesions, there was no leukemic cell infiltration.

Adult↗
PubMed1985

Pulmonary complications in patients with adult T-cell leukemia.

A survey of 360 patients with various hematologic diseases revealed a high frequency of respiratory complications in patients with adult T-cell leukemia (ATL) compared to others. Among 29 patients with ATL, pulmonary complications were seen in 26 patients; leukemic pulmonary infiltration in 13, bleeding in 1, interstitial pneumonitis in 1, and pulmonary infection in 13. The incidence of Pneumocystis carinii and bacterial pneumonias were high despite adequate neutrophil count. Even in chronic and smoldering ATL, respiratory diseases were found in high frequency. Many of those were leukemic cell infiltration. In ten of 13 patients with pulmonary infiltration it occurred in the early stage and 6 of them were diagnosed as having "chronic lung disease" before the diagnosis of ATL. Its histology was accompanied by fibrosis in greater or lesser degree in almost all cases. Transbroncheal lung biopsy (TBLB) is of value in diagnosis (8 of 13 cases).

Adult↗
PubMed1995

An autopsy case of malignant lymphoma with Lyell's syndrome.

We present a case of fatal Lyell's syndrome which developed following a CT examination using omnipaque 3000 contrast medium. A 59-year-old man was suffering from malignant lymphoma. He was readmitted to this hospital due to relapse of fever and lymph node swelling. On the day of readmission, generalized erythema, purpura, and mucosal erosions developed after a CT examination. Steroids and chemotherapy were ineffective, and he expired approximately two weeks after admission. Drug-induced dermatopathy or leukemic cell infiltration in the skin was clinically suspected. Histological findings disclosed toxic epidermal necrolysis.

Autopsy↗
PubMed1990

[Myelofibrosis associated with immunological abnormalities].

A 74-year-old man was admitted to the National Defense Medical College Hospital because of purpura on the extremities. The blood hemoglobin level was 11.5 g/dl, the white blood cell count 7. 3 x 10(9)/l with 3% blastic cells, and the platelet count 4.0 x 10(9)/l. There was leukoerythroblastosis with only mild teardrop appearance of erythrocytes. The blastic cells consisted of two types, megakaryoblast-like cells and myeloblast-like cells. There was a very mild hepatosplenomegaly, but no lymphadenopathies. The bone marrow aspirations yielded dry taps. The marrow biopsy specimen revealed myelofibrosis associated with trilineage hyperplasia, but no apparent infiltration of leukemic cells. Platelet-associated IgG (PAIgG) had a high titer and the response to platelet transfusions was poor. On prednisolone and colchicine, the blastic cells in the peripheral blood disappeared and the platelet count increased. He died of pneumonia. The autopsy showed myelofibrosis with hyperplasia of myeloid and erythroid lineage in the bone marrow. Megakaryocytes were relatively few and there was no infiltration of leukemic cells.

Aged↗
PubMed1980

The acute monocytic leukemias: multidisciplinary studies in 45 patients.

The clinical and laboratory features of 37 patients with variants of acute monocytic leukemia are described. Three of these 37 patients who had extensive extramedullary leukemic tissue infiltration are examples of true histiocytic "lymphomas." Three additional patients with undifferentiated leukemias, one patient with refractory anemia with excess of blasts, one patient with chronic myelomonocytic leukemia, one patient with B-lymphocyte diffuse "histiocytic" lymphoma and one patient with "null" cell, terminal deoxynucleotidyl transferase-positive lymphoblastic lymphoma had bone marrow cells with monocytic features. Another patient had dual populations of lymphoid and monocytoid leukemic cells. The true monocytic leukemias, acute monocytic leukemia (AMOL) and acute myelomonocytic leukemia (AMMOL), are closely related to acute myelocytic leukemia (AML) morphologically and by their response to chemotherapy. like AML, the leukemic cells from the AMMOL and AMOL patients form leukemic clusters in semisolid media. Cytochemical staining of leukemic cells for nonspecific esterases, presence of Fc receptor on the cell surface, phagocytic ability, low TdT activity, presence of surface "ruffles" and "ridges" on scanning EM, elevations of serum lysozyme, and clinical manifestations of leukemic tissue infiltration are features which accompanied monocytic differentiation in these cases.

Adolescent↗
PubMedDate not supplied

Chronic lymphocytic leukemia: changes in bone marrow composition and distribution assessed with quantitative MRI.

The purposes of this study were (a) to determine the prevalence of bone marrow abnormalities in patients with chronic lymphocytic leukemia (CLL) using quantitative MR assessment of axial marrow composition and peripheral marrow distribution; (b) to assess the agreement between both quantitative MR methods and compare their sensitivities to detect marrow alterations; and (c) to correlate MR findings with clinical and laboratory parameters. Twenty-nine consecutive patients with biopsy-proven CLL were investigated on a .5-T MR imager to determine bulk T1 relaxation times of the vertebral bone marrow and proportion of proximal femur surface area occupied by nonfatty marrow on coronal T1-weighted MR images of one hip. Of the 29 patients, 12 (41%) had abnormal increase in lumbar marrow T1 values (>600 msec) and 16 (55%) had increased proportion of surface area occupied by nonfatty marrow in the proximal femur (>+1 SD compared to normal values determined in sex- and age-matched healthy subjects). The results of both quantitative MR methods were normal in 12 patients and abnormal in 11 patients (agreement, 79%). Patients with alterations in peripheral marrow distribution had significantly higher T1 relaxation times (P = .001) than those with normal peripheral marrow. Patients with abnormal marrow composition or distribution at MRI had significantly higher blood and marrow lymphocytosis than patients without these features. In conclusion, the agreement between both quantitative MR methods suggests a parallelism between changes in axial marrow composition and in peripheral marrow distribution in patients with CLL. The limits of quantitative MRI in CLL must be kept in mind, because quantitative MR methods failed to detect leukemic marrow infiltration in 41% of patients.

Adult↗
PubMed1994

Natural killer cell leukemia. An autopsy case.

We describe an autopsy case of natural killer cell leukemia. Leukemic cells appeared morphologically as large granular lymphocytes and expressed a restricted natural killer cell phenotype (CD2, CD38, CD56, HLA-DR). Immunogenotypic analysis revealed germline configurations of TCR-beta, TCR-gamma, and JH genes, indicating a non-T-cell or non-B-cell lineage. These features are consistent with natural killer cell leukemia, a recently proposed clinicopathologic entity. Autopsy findings were characterized by an extremely dense infiltration of leukemic cells in most organs, along with destruction of the normal architecture, corresponding to an aggressive clinical course. Hemophagocytic histiocytosis and an absence of chronic inflammatory reactions caused by recurrent infection in our case are different from morphologic features of CD3+ large granular lymphocytic leukemia. No relationship between Epstein-Barr virus and natural killer cell leukemia was observed.

Female↗