OBJECTIVETo investigate clinical features, diagnosis, therapy, and prognosis in a case of chronic lymphocytic leukemia (CLL) with central nervous system (CNS) invasion.

METHODSThe cellular morphology of bone marrow, cytology and flow cytometry of cells in CSF, and radiographic manifestations were detected in a patient diagnosed as CLL with CNS invasion. The clinical features, pathogenesis, diagnosis,therapy, and prognosis of CLL with CNS invasion were reviewed by literatures.

RESULTSA clonal population of B lymphocytes with typical characteristics of immunophenotype was identified in the patient. After treated with intrathecal chemotherapy, the patient returned to normal cells count of cerebrospinal fluid and normal neurologic status. Previous studies also have demonstrated the efficacy of intrathecal chemotherapy.

CONCLUSIONCNS invasion is a rare complication of CLL. Early detection and treatment may result in better outcomes.

Aged ; Central Nervous System ; pathology ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; pathology ; Leukemic Infiltration ; Male ; Prognosis

Aged, 80 and over ; Exanthema ; etiology ; Female ; Humans ; Leukemia, Monocytic, Acute ; pathology ; Leukemic Infiltration ; complications ; diagnosis ; Skin ; pathology

Leukemia cutis (LC) is defined as a neoplastic leukocytic infiltration of the skin. Few clinical studies are available on recent trends of LC in Korea. The purpose of this study was to analyze the clinical features and prognosis of LC in Korea and to compare findings with previous studies. We performed a retrospective study of 75 patients with LC and evaluated the patients' age and sex, clinical features and skin lesion distribution according to the type of leukemia, interval between the diagnosis of leukemia and the development of LC, and prognosis. The male to female ratio was 2:1, and the mean age at diagnosis was 37.6 yr. The most common cutaneous lesions were nodules. The most commonly affected site was the extremities in acute myelocytic leukemia and chronic myelocytic leukemia except for acute lymphocytic leukemia. Compared with previous studies, there was an increasing tendency in the proportion of males and nodular lesions, and LC most often occurred in the extremities. The prognosis of LC was still poor within 1 yr, which was similar to the results of previous studies. These results suggest that there is a difference in the clinical characteristics and predilection sites according to type of leukemia.
Adult ; Extremities/pathology ; Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*diagnosis/mortality/pathology ; Leukemia, Myeloid, Acute/*diagnosis/mortality/pathology ; *Leukemic Infiltration ; Male ; Neoplasm Staging ; Retrospective Studies ; Skin/*pathology

OBJECTIVETo evaluate the changes of phosphorus metabolites in leukemic infiltration of liver (LIL) with two-dimensional chemical shift imaging(2D CSI)(31)phosphorus MR spectroscopy ((31)P MRS).

METHODSFifteen patients with LIL and 12 healthy subjects (control group) were scanned with liver 2D CSI(31)P MRS by a 1.5T MR Scanner(Sonata, Siemens Corporation). Relative quantification of phosphorus metabolites including phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE) and beta-adenosine- triphosphate (beta-ATP) were detected and after calibrated with model factor, the ratios of PME/PDE, PME/(PME+PDE), PME/ATP, PDE/ATP and Pi/ATP were analyzed.

RESULTSCompared with control group, the PME value, PME/PDE ratio, PME/(PME+PDE) ratio and PME/ATP ratio were increased in LIL group (1.992 +/-0.876 Compared with 1.167 +/-0.427, P <0.05), (0.551 +/-0.339 Compared with 0.254 +/-0.059,P <0.01), (0.326 +/-0.13 Compared with 0.199 +/-0.049, P <0.01)and (1.402 +/-0.654 Compared with 0.792 +/-0.232, P <0.01) respectively.

CONCLUSION(31)P MRS examination can be used as a non-invasive procedure to evaluate the changes of phosphorus metabolites of leukemic infiltration of liver. The increase of PME value and its ratios to PDE, ATP and PME+PDE may indicate leukemic infiltration of liver.

Acute Disease ; Adult ; Aged ; Female ; Humans ; Leukemia ; pathology ; Leukemic Infiltration ; metabolism ; pathology ; Liver ; metabolism ; pathology ; Magnetic Resonance Spectroscopy ; methods ; Male ; Middle Aged ; Phosphorus Isotopes ; metabolism ; Young Adult

OBJECTIVETo evaluate the diagnostic value of bone marrow (BM) involvement detected by F-18-fluorodeoxyglucose-positron emission tomography/computed tomography ((18)F-FDG PET/CT) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

METHODSThe study population comprised 81 consecutive patients with newly diagnosed DLBCL. All patients had both (18)F-FDG PET/CT and standard BM biopsy at iliac crest. In 9 patients, additional direct BM biopsy at FDG-avid bone lesion was performed.

RESULTSAmong all 81 cases, 23 were diagnosed as BM involvement by PET/CT. Of the 23 positive cases 17 were confirmed by biopsy. However, only 11 cases were diagnosed by merely bilateral iliac crest biopsy. In patients in early stage of disease (18)F-FDG PET/CT had the same results as bilateral iliac crest biopsy.

CONCLUSION(18)F-FDG PET/CT is superior to standard BM biopsy in detecting BM involvement in newly diagnosed DLBCL patients. In patients with FDG-avid bone lesions, direct PET/CT-guided bone biopsy seems to be more accurate than standard BM biopsy.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; pathology ; Female ; Fluorodeoxyglucose F18 ; Humans ; Leukemic Infiltration ; diagnostic imaging ; Lymphoma, Large B-Cell, Diffuse ; diagnostic imaging ; pathology ; Male ; Middle Aged ; Positron-Emission Tomography ; methods ; Young Adult

OBJECTIVETo investigate the influence of tissue inhibitor of metalloproteinase 2 (TIMP-2) on the infiltrative patterns of human monocytic leukemic cell line SHI-1 in nude mice.

METHODS1) 1 x 10(7) TIMP-2 gene transduced SHI-1 (SHI-1-TIMP-2) and SHI-1 transduced MSCV gene (SHI-1-MSCV) cells were inoculated via tail vein into 6-week nude mice, which pretreated by splenectomy, cytoxan intraperitoneal injection, and sublethal irradiation(referred as SCI nude mice). 30 days after inoculation, half of the mice were sacrificed, and the infiltration patterns were investigated by histological exam and human CD45 immunohistochemistry, other mice were observed for survival time. 2) Leukemic cells inoculated subcutaneously into the axillary area of mice without any pre-treatment. On day 23 and 30, mice were sacrificed to measure the volume of neoplasm. TIMP-2 protein expression and the micro vein density were detected by immunohistochemistry.

RESULTSIn SCI nude mice inoculated via caudal vein with SHI-1-TIMP-2 cells, the survival time was shorter and infiltration (including in central nervous system) was higher than that in those inoculated with SHI-1-MSCV cells. However, in inoculated subcutaneously group, the neoplasm though grew rapidly at first, over expression of TIMP-2 limited the tumor growth and angiogenesis.

CONCLUSIONThe functions of TIMP-2 are diversity; the role of TIMP-2 in tumor infiltration and metastasis was worthy of further investigation.

Animals ; Cell Line, Tumor ; DNA, Complementary ; genetics ; Genetic Vectors ; Humans ; Leukemia, Experimental ; genetics ; pathology ; Leukemic Infiltration ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; Transfection

Pleural effusion in chronic myeloid leukemia (CML) is poorly understood and rarely reported in the literature. When the pleural effusion is caused by leukemic pleural infiltration, the differential white blood cell count of the effusion is identical to that of the peripheral blood, and the fluid cytology reveals leukemic blasts. We report here a case of bilateral pleural involvement of atypical CML in an 83-yr old male diagnosed with pancreatic cancer with abdominal wall metastasis and incidental peripheral leukocytosis. Based on bone marrow examination, chromosome analysis and polymerase chain reaction he was diagnosed with Philadelphia chromosome negative, BCR/ABL gene rearrangement negative CML. Following 3 months of treatment with gemcitabine for pancreatic cancer, he developed bilateral pleural effusions. All stages of granulocytes and a few blasts were present in both the pleural fluid and a peripheral blood smear. After treatment with hydroxyurea and pleurodesis, the pleural effusion resolved.
Pleural Effusion/*etiology/pathology ; Male ; Leukemic Infiltration/*pathology ; Leukemia, Myeloid, Chronic/complications/*pathology ; Humans ; Aged, 80 and over ; Aged

In order to investigate the relationship between VEGF and matrix metalloproteinase (MMP)-2, -9 in acute myeloid leukemia patients, and evaluate the significance of them in extramedullary leukemic invasion, the expressions of MMP-2 mRNA, MMP-9 mRNA, VEGF mRNA in bone marrow from 86 patients with acute myeloid leukemia (AML), as well as human hematopoietic cell lines were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The proteolytic activities of MMP-2 and MMP-9 in the supernatants were measured by zymography. The VEGF protein in serum of all samples was detected by ELISA. All these results were analyzed for determination of the relationship between VEGF and MMP-2, MMP-9. The results showed that there was a positive correlation between expressions of MMP-2 mRNA or MMP-9 mRNA and VEGF mRNA or protein. But no such correlation was demonstrated in the AML (CR) and normal control (NC) groups. A higher expression level of MMP-2 and MMP-9 in the VEGF positive group was found, as compared with the negative group (P < 0.05). More extramedullary infiltration occurred in VEGF positive groups than that in VEGF negative groups of AML. The expression of bcl-2 in HL-60 cells was upregulated by VEGF. It is concluded that there are significantly positive correlations between the expression of MMP-2 and MMP-9 with VEGF mRNA or protein levels in AML patients. VEGF can upregulate the expression of MMP-2, MMP-9 in HL-60 and a part of the primary leukemic cells. VEGF and MMP-2, MMP-9 may participate in the extramedullary leukemic invasion of AML patients.
Adolescent ; Adult ; Aged ; Female ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Leukemic Infiltration ; Male ; Matrix Metalloproteinase 2 ; biosynthesis ; genetics ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Middle Aged ; RNA, Messenger ; biosynthesis ; genetics ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics

The study was aimed to explore the expression of stromal cell derived factor-1alpha (SDF-1alpha) and its receptor CXCR4, and their relationship with the extramedullary infiltration in acute lymphoblastic, grannulocytic and monocytic leukemia. 66 cases of acute leukemia included 31 cases of acute lymphoblatic leukemia (ALL), 20 cases of acute grannulocytic leukemia (M(2)) and 15 cases of acute monocytic leukemia (M(4)+M(5)). There were 41 cases with extramedullary infiltration and 25 cases without-extramedullary infiltration. Enzyme-linked immunoabsorbent assay (ELISA) and flow cytometry were used to determine expression of SDF-1alpha and CXCR4 respectively on leukemia cells in peripheral blood and bone marrow of different groups. The results showed that average plasma level of SDF-1alpha in the ALL, M(4)+M(5), M(2) patients and the normal control were 1317.87 +/- 220.76, 1339.79 +/- 187.06, 1063.70 +/- 190.74, 1908.34 +/- 135.55 (pg/ml) respectively. The average levels in the ALL, M(4)+M(5) and M(2) patients groups were lower than those in normal control group. Both levels in ALL and M(4)+M(5) patient groups were higher than that in M(2) patient group. The average levels of SDF-1alpha in patient group with extramedullary infiltration and patient groups without-extramedullary infiltration were 1252.49 +/- 263.12, 1234.91 +/- 185.50 (pg/ml) respectively. The former seemed as if higher than the latter, but without statistical significance. The MFI of CXCR4 expression in ALL, M(4)+M(5), M(2) patient group were 78.47 +/- 33.96, 67.21 +/- 24.29, 41.66 +/- 17.18, respectively. CXCR4 expression in ALL and M(4)+M(5) patient groups were higher than that in M(2) patient group (P > 0.05). There was no significant difference between the ALL and M(4)+M(5) patient group (P > 0.05). The MFI of CXCR4 expression in patients with extramedullary infiltration and patients without extramedullary infiltration were 81.72 +/- 27.63, 36.94 +/- 11.86 respectively. The former was higher than the latter (P < 0.05). It is concluded that the higher expression of CXCR4 on acute lymphoblatic and monocytic leukemia cells may be one of the molecular mechanisms of extramedullary infiltration in both kinds of leukemia. The average plasma levels of SDF-1alpha decreased in leukemia patients and this decrease not related to the extramedullar infiltration, which may be due to the SDF-1alpha local expression in the organ infiltrated.
Acute Disease ; Adolescent ; Adult ; Chemokine CXCL12 ; Chemokines, CXC ; biosynthesis ; genetics ; Child ; Child, Preschool ; Female ; Humans ; Leukemia ; metabolism ; pathology ; Leukemia, Myeloid, Acute ; metabolism ; pathology ; Leukemic Infiltration ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; Receptors, CXCR4 ; biosynthesis ; genetics ; Stromal Cells ; metabolism

OBJECTIVETo study the expression of CXCR4 in acute leukemic cells and its clinical significance.

METHODBone marrow samples from 73 acute leukemia patients and leukemic cell lines were investigated by flow cytometry (FCM), the expression of SDF-1 in human marrow stromal cells and meninges were studied by using reverse transcription polymerase chain reaction (RT-PCR). Adhesion, migration and invasion of U937, NB4 and K562 cells were studied in vitro.

RESULTSThe expression rates of CXCR4 in ALL and AML patients was 65.6% and 17.1%, respectively. And it was 0.2%, 41.0% and 52.0% in K562, U937 and NB4 cells, respectively. The extramedullary infiltration rates were 61.9% and 18.2% for CXCR4 positive and negative groups of ALL, respectively (P < 0.05); while in AML, the number of peripheral white blood cells in CXCR4 positive group was lower than that in CXCR4 negative group (P < 0.05). SDF-1alpha could enhance the adhesion, migration and invasion capacity of leukemic cells in vitro.

CONCLUSIONOverexpression of CXCR4 in AL cells might be the molecular mechanism of extramedullary infiltration in leukemia.

Acute Disease ; Adolescent ; Adult ; Aged ; Bone Marrow Cells ; metabolism ; pathology ; Cell Adhesion ; Cell Line, Tumor ; Cell Movement ; Chemokine CXCL12 ; genetics ; Female ; Fibroblasts ; metabolism ; pathology ; Flow Cytometry ; Gene Expression Regulation, Neoplastic ; Humans ; K562 Cells ; Leukemia ; genetics ; metabolism ; pathology ; Leukemic Infiltration ; metabolism ; pathology ; Male ; Meninges ; metabolism ; pathology ; Middle Aged ; Receptors, CXCR4 ; biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; U937 Cells