Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Resistance, Neoplasm/drug effects , Lymphoma, Non-Hodgkin/drug therapy , Neoplasm Recurrence, Local/drug therapy , Salvage Therapy , Adult , Aged , Aged, 80 and over , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Follow-Up Studies , Humans , Lymphoma, Non-Hodgkin/mortality , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Prognosis , Survival Rate , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine , Young Adult , GemcitabineABSTRACT
A bone marrow examination in a young woman with anemia and ß-thalassemia trait showed dyserythropoiesis in less than 10% of erythroblasts without other myelodysplastic changes, and cytogenetic analysis revealed trisomy of chromosome 8. Although she did not fulfill the current World Health Organization (WHO) criteria for diagnosis of a myelodysplastic syndrome, her acquired bone marrow disorder behaved as such, and she later developed acute myeloid leukemia.
Subject(s)
Early Detection of Cancer/methods , Myelodysplastic Syndromes/diagnosis , Pancytopenia/diagnosis , Cytogenetic Analysis , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/genetics , Pancytopenia/complications , Pancytopenia/genetics , Young AdultABSTRACT
AIMS: Asteroid B cells are a component of normal thymus. It is currently unclear whether these cells are identifiable in T cell lymphoblastic leukaemia/lymphoma (T-ALL/LBL) of the thymus. The aim of this study was to identify asteroid B cells both in thymic and extrathymic tissue involved by T-ALL/LBL. METHODS AND RESULTS: Thymic, lymph node (LN) and bone marrow trephine biopsy (BMTB) samples from eight patients with T-ALL/LBL were reviewed. All had been investigated by immunohistochemistry and one by fluorescent in situ hybridization (FISH). The BMTB samples of two of eight T-ALL/LBLs and LN sample in one of them showed the presence of asteroid-shaped B cells with dendritic cytoplasmic processes. These B cells also expressed CD23 and the features were akin to the unique thymic asteroid B cells. Both patients had aggressive/resistant disease. Cytogenetic analysis in one showed a complex translocation involving the T cell receptor beta (TCRB) gene at 7q35 and a distal region of 9q known to harbour the NOTCH1 gene. CONCLUSION: This is the first report of T-ALL/LBL documenting the presence of an asteroid B cell-rich microenvironment at bone marrow and LN sites. In this small subset, T-ALL/LBL cells are possibly dependent upon asteroid B cells, and whether targeting of asteroid B cells with anti-CD20 monoclonal antibody in such cases will result in clinical benefit remains to be determined.
Subject(s)
B-Lymphocytes/pathology , Bone Marrow/pathology , Lymph Nodes/pathology , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Thymus Gland/pathology , B-Lymphocytes/immunology , Bone Marrow/immunology , Bone Marrow Cells/immunology , Bone Marrow Cells/pathology , Humans , In Situ Hybridization, Fluorescence , Lymph Nodes/immunology , Male , Middle Aged , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/immunology , Thymus Gland/immunologySubject(s)
Leukemia-Lymphoma, Adult T-Cell/pathology , Anemia/etiology , Antigens, CD/analysis , Blood Cells/pathology , Bone Marrow Cells/pathology , Bone Marrow Examination , Humans , Hypercalcemia/etiology , Leukemia-Lymphoma, Adult T-Cell/blood , Leukemia-Lymphoma, Adult T-Cell/complications , Lymphocytes/ultrastructureABSTRACT
A young man presented with systemic symptoms and marked eosinophilia. Subsequently cyclical weight gain and edema contributed to a diagnosis.
Subject(s)
Eosinophilia/diagnosis , Adult , Angioedema , Cell Count , Eosinophils/pathology , Follow-Up Studies , Humans , Male , Weight GainABSTRACT
The alpha-helical amphipathic peptide D-(KLAKLAK)2 is toxic to eukaryotic cells if internalized by a suitable targeting mechanism. We have targeted this peptide to malignant hemopoietic cells via conjugation to monoclonal antibodies, which recognize lineage-specific cell surface molecules. An anti-CD19/peptide conjugate efficiently killed 3/3 B lymphoid lines. However, an anti-CD33/peptide conjugate was cytotoxic to only one of three CD33-positive myeloid leukemia lines. The IC50 towards susceptible lines were in the low nanomolar range. Conjugates were highly selective and did not kill cells that did not express the appropriate cell surface cognate of the antibody moiety. Anti-CD19/peptide conjugates efficiently killed cells from patients with chronic lymphocytic leukemia but anti-CD33/peptide reagents were less effective against fresh acute myeloid leukemia cells. We therefore suggest that amphipathic peptides may be of value as targeted therapeutic agents for the treatment of a subset of hematologic malignancies.
