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PubMed1989

[The role of leukemic conversion in the development of lymphoma infiltration of the nervous system].

On the basis of neuropathologic studies in 22 patients died from ML it was found that lymphoma cells in the brain and spinal cord were in the form of leukostasis, infiltrations usually limited to perivascular spaces, infiltrations in hemorrhagic foci and their vicinity. In cerebrospinal meninges, spinal roots and peripheral nerves we observed leukostasis and intraparenchymatous infiltrations. It was found that the most important role in the development of lymphoma infiltrations in the nervous system was played by hematogenic metastases whose development in the brain and spinal cord was promoted by leukemic conversion with high leukocytosis. In contrast, marked dissemination of lymphoma cells to peripheral blood is not indispensible for the development of infiltrations in the cerebrospinal meninges and peripheral nervous system.

Acute Disease↗
PubMed1997

Leukemic cells within skin lesions of psoriasis in a patient with acute myelogenous leukemia.

We report on an 81-year-old man with acute myelo-monocytic leukemia (FAB M4) and a long-standing history of psoriasis. Biopsy of psoriatic plaques revealed the coexistence of characteristic histopathologic aspects of psoriasis together with an infiltrate of blasts with features of myelo-monocytes, suggestive of a specific leukemic infiltrate within plaques of psoriasis. Immunohistologic stainings showed positivity of blasts for LN2 (CD74), MT1 (CD43), and lysozyme, consistent with a myeloid lineage of these cells. To the best of our knowledge, this is the first report on the association of psoriasis with myelogenous leukemia. The presence of leukemic cells within psoriatic skin plaques may be explained by non-specific recruitment of recirculating malignant cells to the skin. Alternatively, as psoriasis is an inflammatory disease involving granulocytes among other cell types, it may be hypothesized that leukemic cells retain to some extent their capability to respond to physiologic stimuli and enter the skin in response to specific chemotactic factors.

Aged↗
PubMed1992

Acute promyelocytic infiltration of the optic nerve treated by oral trans-retinoic acid.

BACKGROUND: Oral trans-retinoic acid has recently been shown to be an effective treatment modality for acute promyelocytic leukemia. This type of drug differs from traditional tumoricidal agents by promoting differentiation of the malignant, immature cells. METHODS: The authors describe a patient with optic nerve infiltration by acute promyelocytic leukemia documented ophthalmoscopically and confirmed by standardized echography and magnetic resonance imaging. High-resolution chromosome banding revealed the patient had a 15;17 chromosomal translocation known to be associated with acute promyelocytic leukemia. Treatment was instituted with oral all trans-retinoic acid without adjuvant radiotherapy or intrathecal chemotherapy. RESULTS: Results of serial bone marrow examination showed progressive differentiation of malignant cells with complete bone marrow remission. Results of serial ophthalmic examinations showed complete resolution of the leukemic optic nerve head infiltration. CONCLUSION: All trans-retinoic acid alone can be an effective treatment for optic nerve head infiltration in acute promyelocytic leukemia. This case suggests that radiation therapy may not be necessary in acute promyelocytic leukemia with optic nerve infiltration.

Administration, Oral↗
PubMed1993

Discordant LFA-1/ICAM-1 expression in a case of secondary plasma cell leukemia associated with subcutaneous plasmacytoma.

We observed a unique case of multiple myeloma that was transformed into plasma cell leukemia presenting with subcutaneous and soft tissue infiltrates. Subcutaneous and minor pelvic soft tissue plasmacytomas and the leukemic transformation were diagnosed in a 72-year-old woman after she had completed 9 months of chemotherapy for IgG kappa multiple myeloma. Immunophenotypic study revealed that leukemic cells in her peripheral blood were positive for ICAM-1 (CD54) but negative for LFA-1 alpha (CD11a) and LFA-1 beta (CD18), whereas infiltrating leukemic cells in the subcutaneous plasmacytoma of the left thigh were positive for LFA-1 alpha and LFA-1 beta but negative for ICAM-1. In addition, intermingling capillary endothelial cells were positive for ICAM-1. Extramedullary soft tissue plasmacytoma is uncommon in association with plasma cell tumors, and the exact mechanism of the development of plasmacytoma is not known. In the present case, however, the discordant expression of LFA-1/ICAM-1 adhesion molecules may have accounted for the distinct patterns of growth and the spread of the subcutaneous plasmacytoma through homing of the LFA-1 alpha+, LFA-1 beta+ leukemic cells to ICAM-1+ endothelial cells.

Aged↗
PubMedDate not supplied

Chest radiographic-pathologic correlation in adult leukemia patients.

A radiographic-pathologic correlation study of adult leukemia patients was conducted to determine the frequency and radiographic appearance of leukemic involvement and related complications within the chest. One hundred thirteen autopsy protocols were examined. Radiographic correlation was obtained in 60 of these cases. Autopsy pulmonary findings included hemorrhage in 74% of the cases, infectious infiltrates in 67%, edema or congestion in 57%, and leukemic infiltration in 26%. Only 5% of the chest radiographs were normal. Alveolar or interstitial abnormalities were identified in 90%, pleural effusion in 40%, and lymphadenopathy in 17%. Correlation demonstrated pulmonary infection to be by far the most common cause of radiographic opacity. Because of its frequent occurrence, high associated mortality, and potential reversibility, pneumonia must always be considered first in the differential diagnosis of radiographic opacity in these patients.

Adult↗
PubMed1984

Monocytic leukemia in a horse.

On clinical examination, a six-year-old Hassian gray gelding with a history of impaired performance, slight cough, colic, and edema of the ventral abdomen, prepuce and the legs had reduced skin turgor, pale mucous membranes, forced costoabdominal breathing, reduced venous return, enlarged lymph nodes, and splenomegaly. Hematologic findings revealed anemia, leukocytosis and a high percentage of monocytoid leukemic cells. Generalized lymphadenopathy, splenomegaly, ascites, hydrothorax, and a diffusely thickened gut wall were found at necropsy. Massive infiltration with monocytoid leukemic cells was detected in lymph nodes, spleen, bone marrow, liver, gut wall, kidneys, and choroid plexus. Incubation of living cells obtained from a leukocyte concentrate with latex particles revealed phagocytosis in the leukemic cells on light and electron microscopy. The leukemic cells also had a marked alpha-naphthyl-acetate and naphthol-AS-acetate esterase activity, but were only weakly positive to naphthol-AS-D-chloroacetate esterase. A very weak alkaline phosphatase activity only was demonstrated in a few leukemic cells. On scanning electron microscopy, the leukemic cells had prominent ruffles and ridge-like profiles. These features of the leukemic cells excluded lymphocytic and granulocytic leukemia, and monocytic leukemia was diagnosed.

Alkaline Phosphatase↗
PubMed1986

Leukopenic chronic T cell leukemia mimicking hairy cell leukemia: association with human retroviruses.

We report two cases of a T cell lymphoproliferative disease not previously described, with cytologic and clinical features similar to those associated with Galton's "prolymphocytic" leukemia (PL). Our patients, like those with Galton's PL, had massive splenomegaly and minimal or absent hepatomegaly and lymphadenopathy. In contrast, however, our patients had leukopenia, as well as low percentages of leukemic cells in the peripheral blood and in the bone marrow. In splenic imprints, the nuclear chromatin pattern of most of the leukemic cells was intermediate between those of mature lymphocytes and those of lymphoblasts, and the nuclei contained single, centrally located, conspicuous nucleoli. In sections of the spleen, the leukemic cells diffusely infiltrated the red pulp in a pattern strikingly similar to that of hairy cell leukemia; however, when the leukemic cells were studied cytochemically, the cytoplasmic acid phosphatase positivity was punctate and tartrate-sensitive. The leukemic cells were sheep erythrocyte rosette-positive and expressed T cell-associated antigens. Initially, both patients responded well to therapeutic splenectomy. One patient received combination chemotherapy after splenectomy and is alive and well 24 months after diagnosis. The other patient was in complete clinical remission for one year after splenectomy and received chemotherapy at relapse. He died, however, 23 months after splenectomy, with disseminated disease. IgG antibody titers against human T lymphotropic virus type I (HTLV-I) were detected in one patient and against HTLV-II in the other. The leukemia in these patients represents a distinct clinicopathologic entity within the spectrum of peripheral T cell lymphoproliferative diseases that includes Galton's PL of T cell derivation, T cell chronic lymphocytic leukemia, T cell hairy cell leukemia, and adult T cell leukemia/lymphoma.

Adult↗
PubMed2001

Clinical significance of magnetic resonance imaging of bone marrow in patients with leukemia.

To investigate the clinical significance of magnetic resonance imaging (MRI) of bone marrow in patients with acute leukemia, the femoral and pelvic marrow were evaluated by using MRI with a T1-weighted spin-echo (SE) method and a short T1 inversion recovery (STIR) technique. Normal bone marrow examination was performed with coronal T1-weighted MRI of pelvis and femurs, and showed persistent red marrow. There was a bright signal of fatty marrow in the femoral epiphyses and apophyses. MRI pattern of bone marrow in the 54 cases of acute leukemia showed abnormal signal patterns of femoral and pelvic marrow: (1) grade I (n = 4), (2) grade II (n = 11), (3) grade III (n = 8), (4) grade IV (n = 17), and (5) graded V (n = 14). Leukemic cells had infiltration onseted by red marrow in adult patients with leukemia. The marrow of femur had infiltration from diaphysis to epiphysis, and to femoral head and greater trochanter. The lower grades (grade IV, V) of leukemic marrow supported the diagnosis of AML in MRI, which achieved higher complete remission. The adult patients with ALL had higher grades (grade I-III) in MRI. Our findings indicated that MRI of femoral marrow is an important tool for accurate diagnosis and management of patients with leukemia that may function as an adjunct to bone marrow aspiration and biopsy. The pattern of MRI in patients with newly diagnosed leukemia predicted the prognosis and CR of leukemia.

Adult↗
PubMed2001

A minor E-selectin ligand, CD65, is critical for extravascular infiltration of acute myeloid leukemia cells.

Adhesive ligands on acute myeloid leukemic (AML) blasts may mediate transmigration and extravascular infiltration. In this study, 30 AML samples were examined for expression and density of adhesion antigens. By univariate analysis, four patients with extravascular infiltration showed significantly higher expression of CD2, CD11a, CD11b, CD11c, CD15, CD65, CD86, and HLA-DR as compared with patients without infiltration. These four patients also showed significantly higher density of CD11a, CD11b, CD11c, CD15 and CD65 expression. By multivariate analysis, CD65 expression was the only significant independent risk factor for infiltration, suggesting that this is a critical adhesion molecule for extravascular AML infiltration.

Acute Disease↗
PubMed1999

Sinus polyp-associated soft tissue lesion and unilateral blindness: complications of extraction in leukemic patient.

A case of an inflammatory polyp-associated lesion extending through an extraction socket appearing as an intraoral nodular lesion and unilateral blindness secondary to leukemic optic nerve head infiltration is reported. The patient was a 28-year-old male whose his upper first molar had been extracted fifteen days previously. The lesion was an asymptomatic soft tissue mass, red in color and hot tender to palpation, involving the alveolar ridge in the maxillary molar area. Although this is apparently a rare occurrence, the nature of the lesion was suggested by the history, clinical appearance, and radiographic findings. Excision of the inflammatory lesion was followed by complete healing with closure of the lesion. Unfortunately, the blindness was irreversible. The patient is still under leukemia therapy. Review of the literature did not yield any other such cases. The role of oral lesions as a diagnostic indicator and the importance of dental surgeons in the diagnosis of leukemic patients are discussed. It is concluded that proper precautions and meticulous early diagnosis are required in these patients and that dental practitioners should be aware of the diagnostic features and possibilities of oral complications associated with leukemia.

Adult↗
PubMed1998

Association of v-Ha-ras transgene expression with development of erythroleukemia in Tg.AC transgenic mice.

A transgenic mouse line (Tg.AC) carrying an activated v-Ha-ras oncogene fused to the embryonic zeta-globin promoter develops an array of spontaneous epithelial and mesenchymal neoplasms. In this report we describe the morphological, immunophenotypic, and molecular features of a unique hematopoietic neoplasm in these mice. The cardinal lesion of this disease is marked hepatomegaly due to leukemic proliferation and infiltration. In the peripheral blood, there is a marked increase in the number of metarubricytes and other less differentiated erythroid progenitor cells. Leukemic cells stain positively with an erythroid-associated nuclear transcription factor (GATA-1). Using a reverse transcription polymerase chain reaction assay, co-expression of GATA-1 and endogenous zeta-globin genes is detected in hematopoietic tissues of nonleukemic transgenic and nontransgenic mice. ras transgene expression is, however, detected only in normal bone marrow and leukemic tissues of transgenic mice, and 5' mapping experiments using S1 protection analysis of total RNA from leukemic tissue indicates that transcription of the transgene mRNA is initiated from the natural zeta-globin promoter start site, supporting the belief that the zeta-globin promoter directs v-Ha-ras expression in erythroid progenitor cells, ultimately leading to leukemic transformation.

Animals↗
PubMed1995

[An animal model of leukemogenesis using transgenic mice].

The bcr/abl chimeric oncoprotein is considered to be implicated in the pathogenesis of Philadelphia chromosome-positive human leukemias. To investigate its biological function and the role in leukemogenesis in vivo, we generated transgenic mice expressing p210bcr/abl driven by the metallothionein promoter. Two of six founder mice and the transgenic progeny of one leukemic founder mouse developed leukemias several months after birth. Phenotypically, each leukemic mouse showed a thymic enlargement, a marked splenomegaly, and/or lymphnode swellings. Pathological examination revealed that leukemic cells were infiltrated in all tissues examined, especially in thymus, spleen, liver, and lymphnode. Expression of the p210bcr/abl transgene product and increased phosphorylation of cellular proteins in leukemic tissues were detected by the Western blot analysis. In addition, the expressed p210bcr/abl protein was demonstrated to possess an enhanced kinase activity by the in vitro immunecomplex kinase assay. These results indicate that hematopoietic precursor cells expressing the p210bcr/abl transgene product acquired a proliferative advantage and eventually developed leukemias in transgenic mice. The p210bcr/abl transgenic mice are considered to be an excellent animal model to investigate p210bcr/abl function and its role in leukemogenesis in vivo.

Animals↗
PubMed1990

[A case report of acute leukemia following the onset of cerebral sinus thrombosis].

A case was reported in which the patient, whose leukemic cells were not found in the peripheral blood, died several days after the onset of cerebral sinus thrombosis, and after the autopsy acute leukemia was diagnosed. The patient, a 68-year-old female, was admitted with clouding of the consciousness. In the initial examination, she was semicomatose, pendulum-like movement was seen in the eyeballs, and hemorrhagic maculae on the trunk and extremities. Among the laboratory findings, WBC was 8, 100 (B 1, St 6, S 77, L 14, Mon 2), RBC 375 x 10(4), Hb 12.5, Ht 37, PLT 3.5 x 10(4), PT 15.6, PTT 68, Fib 158, FDP 10 and AT-III 75. In contrast enhanced CT, an empty triangular sign was observed. On the third hospital day, the patient died of a cerebral hernia. On autopsy, thrombosis was found in the bilateral sigmoid sinus. In the cerebral tissue, congestion was throughout the brain, and many leukemic cells were seen in the dilated blood vessels, but there was no infiltration into the parenchyma. The bone marrow, hypercellular, showed many intermediate type and blastic myeloid cells. The main neurological complications of leukemia are leukemic infiltration and intracranial hemorrhages. Capillary obstructions associated with the disseminated intravascular coagulation (DIC) syndrome are rarely experienced, but obstructions of thick arteries or thick veins such as venous sinuses are seldom seen in general, and most reports of such cases were those resulting from chemotherapy after making a diagnosis of acute leukemia. In the literature, there have been only two reports in our literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2006

Hypoxia inducible factor-1alpha and leukemic cell differentiation.

Arsenic trioxide (As2O3, ATO) is a recently developed drug for the effective treatment of acute promyelocytic leukemia (APL). Experimental studies showed that in vitro differentiation-inducing ability on APL cells of this drug is not significant compared with its in vivo activity. We unexpectedly found recently that hypoxia-mimetic agents and moderate real hypoxia triggered acute myeloid leukemic cells to undergo differentiation. Furthermore, intermittent hypoxia significantly prolonged the survival of the transplanted leukemic mice with inhibition of infiltration and induction of differentiation of leukemic cells. In the following works, molecular mechanisms of hypoxia-induced differentiation were investigated and some interesting results have been obtained. This review will shortly summarize the related progresses and discuss the questions remained to be further investigated.

Animals↗
PubMed1990

[Successful bronchial arterial infusion (BAI) of ACNU in the treatment of pulmonary infiltration of acute non-lymphocytic leukemia (ANLL) cells].

A 35-year-old man was admitted to our hospital because of lumbago on March 25, 1988. On admission white blood count was 1,200/microliters with neutrophils of 9% and lymphocytes of 91%, hemoglobin level was 11.2g/dl and platelet count was 55 x 10(3)/microliters. Bone marrow smear showed 77% leukemic cell including non-specific or specific esterase-positive cells. Chest X-rays showed the presence of mediastinal tumor and diffuse reticular shadows. A diagnosis of ANLL was made and a hematological remission was obtained after one course of combination chemotherapy consisting of BH-AC, daunorubicin and prednisolone, but the enlarged mediastinal tumor and pulmonary infiltration worsened rapidly followed by marked dyspnea. This radiographic abnormal shadow was confirmed to be leukemic infiltration from the finding of transbronchial lung biopsy. We hesitated to give systemic chemotherapy because he also had had liver abscess. Accordingly we performed BAI of ACNU at a dosage of 150 mg which led to a dramatic improvement in dyspnea. 60Co therapy was performed on the mediastinal tumor. On May 30, when he had a relapse, he was unsuccessfully treated with systemic chemotherapy. The leukemic cells invaded most of the organs and the patient died on July 19, 1988. It is likely that BAI of ACNU for leukemic pulmonary infiltration was effective.

Adult↗
PubMed1990

Establishment and characterization of a leukemic murine cell line derived from MCF 247 MuLV-induced T-cell lymphoma.

Understanding of the leukemic evolution of human non-Hodgkin's lymphomas is hindered by the lack of appropriate animal models. For this purpose, a highly leukemic cell line NQ22, derived from a MCF 247 murine leukemia virus (MuLV)-induced murine T-cell lymphoma, was established, and its preliminary characterization is described. The NQ22 cell line is easily transplantable subcutaneously (s.c.) into syngeneic AKR mice exhibiting early peripheral blood invasion and widespread dissemination with a leukemic pattern of infiltration. Such peculiar in vivo behavior is a stable phenotypic feature, probably determined genetically. Biological and differentiation characteristics of the NQ22 cell line were analyzed and compared to those of other non-leukemic T-lymphoma lines. In addition, no evidence of possible involvement of plasminogen activator (PA) enzymes and of their inhibitors (PAI) in the spreading ability of NQ22 cells was observed.

Animals↗
PubMed2000

[Monitoring minimal residual disease in patients with hairy cell leukemia in complete remission after treatment with 2-chlorodioxyadenosine].

Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA) induces in 85% patients complete remission. Complete remission is defined as the condition when signs of activity of the disease are absent, splenomegaly and lymphadenopathy are absent, the hemoglobin concentration is > or = 120 g/l, the absolute number of granulocytes is > or = 1.5 x 10(9)/l and the number of thrombocytes is > or = 100 x 10(9)/l. In complete remission in the peripheral blood, bone marrow aspirate and bioptic samples obtained by trephin bone marrow core biopsy, using standard staining (hematoxylin-eosin and May-Grünwald-Giemsa's method), no leukemic cells are present. When more sensitive methods are used (immunophenotyping, immunohistochemistry or molecular genetic methods), a persisting leukemic population can be detected which is described as minimal residual disease (MRD). For detection of MRD the authors used immunohistochemical examination of bone marrow with DBA.44 antibodies. As leukemic cells they described those which produced intense cytoplasmic and membrane positivity with antibody DBA.44 and corresponded morphologically to hairy cells. For evaluation computer analysis of the picture LUCIA-M was used. The infiltration grade was examined on three areas of standard size (3 x 65,265 micron 2) and expressed in percent. A total of 45 trepanobioptic specimens from 21 patients were examined who achieved after treatment with 2-CdA complete remission. In all samples suitable for evaluation the presence of leukemic cells (MRD) was detected with a median of 3% and a range of 1% to 18%. With induction of complete remission correlates also the low serum level of the soluble receptor for IL-2 (sIL-2R). In a female patient after 24 months of treatment with 2-CdA the grade of leukemic infiltration rose from 1% to 12% and during the 36th month to 50% DBA.44+ leukemic cells. The incipient relapse in this patient was not associated, despite marked infiltration of bone marrow, with failure of hematopoiesis and a marked rise of sIL-2R.

Adult↗
PubMed1994

Growth of sensitive and drug-resistant human myeloid leukemia cells in SCID mice.

Drug resistance is a critical problem in the therapy of hematologic malignancies. Recent advances in the transplantation of human normal and transformed hematopoietic cells into severe combined immunodeficient (SCID) mice provide an opportunity to study the biologic and molecular events that mediate resistance. We studied the engraftment of several human myelogenous leukemia cell lines sensitive and resistant to amsacrine (mAMSA), vincristine, hycamptamine, methotrexate, or doxorubicine (KBM3/AMSA, K562/Vcr, HL60/Hy10, K562/MTX, HL60/Dox). The distribution and growth potential of these cells was evaluated using molecular and histologic techniques. Inoculation of 2 x 10(7) leukemic cells led to manifestation of disease, and subsequent tissue analysis showed evidence of leukemia. The survival of mice varied from 21 to 135 days. Terminally, the animals showed symptoms of wasting, development of local tumors, or both. Massive leukemic dissemination with infiltration of bone marrow and various organs including lungs, spleen, liver, ovaries, and brain was detected in most cases. No differences were observed in the tissue distribution of sensitive as compared to resistant leukemia cells. These findings demonstrated that human leukemic cells retain, in SCID mice, the clinico-pathologic picture of the original disease in humans. The development of numerous drug-resistant phenotypes in vitro does not alter the subsequent behavior of resistant cells in vivo when compared with sensitive counterparts. The levels of resistance are not modified by passage through SCID mice. This model offers an opportunity for developing new preclinical in vivo systems for modulation of drug resistance, and the combination of this in vivo model with gene transfer methods will also provide an important system for testing the molecular alterations involved in drug resistance and leukemic progression.

Acute Disease↗