title: [LAT (linker for activation of T cells): a useful marker for megakaryocyte evaluation on bone marrow biopsies].
abstract: Detection of atypical megakaryocytes in bone marrow biopsies, especially in cases of myelodysplastic syndromes (MDS), chronic myeloproliferative disorders (CMPD) and acute leukemias, is facilitated by staining for markers such as Ulex europaeus agglutinin (UEA)-J, CD31, CD61 and von Willebrand factor (VWF), the latter being considered the most sensitive. Recently, LAT (linker for activation of T cells), a molecule involved in T-cell activation and platelet aggregation, was found to be expressed by megakaryocytes and platelets in tissue sections. We compared VWF and LAT immunoreactivity on megakaryocytes in 64 bone marrow biopsies from 12 normal controls (NC), and from patients with MDS (n=18), CMPD (n=21) and acute megakaryocytic leukemia (AML-M7, n=13). Immunostaining was performed on paraffin sections with polyclonal antibodies against VWF and LAT. Immunoreactivity was evaluated by counting positive megakaryocytes in 10 high-power fields, and values were compared using Student's t test for paired data. Both VWF and LAT predominantly stained the cytoplasm of megakaryocytes, although LAT was also recognizable on the cell membrane. In most biopsies, the immunoreactivity of the two antibodies was quite similar. No significant differences were noticed between the mean values of VWF+ and LAT+ megakaryocytes. However, in 22 cases (5 NC; 5 MDS; 6 CMPD; 6 AML-M7), the number of LAT+ megakaryocytes was at least 30% higher than VWF+cells, while in 3 cases opposite findings were found. In 3 AML-M7 cases, anti-LAT antibodies stained numerous megakaryocytes, but anti-VWF staining was practically negative; in another 5 AML-M7 cases, anti-LAT labeling was much stronger than anti-VWF staining. LAT represents a useful immunohistochemical marker for megakaryocytes in normal and pathological conditions. It seems to be expressed by megakaryocytes more than VWF in most cases and, particularly, in conditions associated with poorly differentiated megakaryocytes, such as acute megakaryocytic leukemias. The use of LAT staining should be recommended in association with other megakaryocyte markers in the study of bone marrow biopsies in cases of hematopoietic disorders.
authors.affiliation: Anatomia Patologica ", Università degli Studi di Brescia, Spedali Civili Brescia, P.le Spedali Civili 1, I-25124 Brescia, Italia.
authors.forename: M
authors.initials: M
authors.lastname: Ungari
authors.forename: W
authors.initials: W
authors.lastname: Pellegrini
authors.forename: E
authors.initials: E
authors.lastname: Borlenghi
authors.forename: D
authors.initials: D
authors.lastname: Marocolo
authors.forename: A
authors.initials: A
authors.lastname: Ubiali
authors.forename: C
authors.initials: C
authors.lastname: Agazzi
authors.forename: A
authors.initials: A
authors.lastname: Pich
authors.forename: V
authors.initials: V
authors.lastname: Franco
authors.forename: F
authors.initials: F
authors.lastname: Facchetti
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis*; D003593:Cytoplasm / Q000737:chemistry; D005169:Factor VIII / Q000032:analysis; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007947:Leukemia, Megakaryoblastic, Acute / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000737:chemistry / Q000473:pathology; D008297:Male; D008533:Megakaryocytes / Q000737:chemistry*; D008565:Membrane Proteins; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000378:metabolism / Q000473:pathology; D016612:Paraffin Embedding; D010750:Phosphoproteins / Q000032:analysis*; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C110810:LAT protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; D014841:von Willebrand Factor; D005169:Factor VIII