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1.
Am J Hematol ; 67(1): 34-41, 2001 May.
Article in English | MEDLINE | ID: mdl-11279655

ABSTRACT

Acute promyelocytic leukemia (APL) has a favorable prognosis. Current therapy includes chemotherapy used in combination with all-trans-retinoic acid (ATRA). Although the differentiating effects of ATRA on promyelocytes have been well established, in vitro studies have shown that less-differentiated APL blasts (CD34(+)) demonstrate a variable responsiveness to ATRA. To assess the clinical relevance of this finding, we analyzed a cohort of 38 patients with t(15;17) and/or PML-RARalpha APL to determine the incidence and laboratory features of CD34(+) APL. Thirty-two percent (12/38) of cases were CD34(+). There was a difference in WBC at presentation between CD34(+) and CD34(-) cases (34.6 +/- 9.2, mean +/- standard error vs. 5.4 +/- 2.0, P = 0.009). Patients with CD34(+) APL demonstrated a micro/hypogranular phenotype (75%) (P = 0.001), co-expression of CD2(+) (83%) (P = 0.001), and the bcr3 isoform (100%) (P = 0.017). In contrast, CD34(-) cases demonstrated hypergranular morphology (65%), CD2(+) (15%), and the bcr1 isoform (50%). A high presenting WBC count (\G10 x 10(9)/L) was associated with an inferior overall survival (Log rank = 0.0047). Patients with CD34(+) APL demonstrated an incidence of early mortality of 50%. Despite a marked correlation between CD34 positivity and increased WBC count, overall survival of CD34(+) and CD34(-) cases did not differ significantly in our small cohort. Immunophenotypic analysis for CD34 expression should be included in future large APL trials to determine if detection of CD34(+) blasts represents an independent adverse prognostic factor.


Subject(s)
Antigens, CD34/analysis , Leukemia, Promyelocytic, Acute/immunology , Leukemia, Promyelocytic, Acute/pathology , Protein-Tyrosine Kinases , Proto-Oncogene Proteins , Actuarial Analysis , Adolescent , Adult , Aged , CD2 Antigens/biosynthesis , Cohort Studies , Female , Granulocytes/pathology , Humans , Immunophenotyping , Karyotyping , Leukemia, Promyelocytic, Acute/diagnosis , Leukocytosis/pathology , Male , Middle Aged , Neoplasm Proteins , Oncogene Proteins/biosynthesis , Oncogene Proteins, Fusion , Prognosis , Protein Isoforms/biosynthesis , Proto-Oncogene Proteins c-bcr , Survival Rate , Translocation, Genetic
3.
Am J Hematol ; 56(3): 131-42, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9371524

ABSTRACT

Early diagnosis of t(15;17) acute promyelocytic leukemia (APL) is essential because of the associated disseminated intravascular coagulation and the unique response of the disease to all-trans retinoic acid (ATRA) therapy. Early diagnosis depends primarily on morphological recognition. The French-American-British (FAB) classification, however, does not describe all morphological variations that occur in APL. In 25 cases with evidence of APL confirmed by cytogenetic and/or molecular analysis, we found a heterogeneous morphological group. The most common form of APL was heterogeneous and consisted of various combinations of cells in which hypergranular cells and some cells with multiple Auer rods were obvious. In some cases, one cell predominated. This led to the description of five subcategories. These included the classical FAB M3 with hypergranular cells and multiple Auer rods; the FAB variant with hypogranular bilobed cells; the basophilic cell type of McKenna et al. [Br. J. Haematol 50:201, 1982]; and two additional subtypes, one consisting of differentiated promyelocytes and a few blast cells (M2-like), and the other consisting largely of blast cells and a few early promyelocytes (M1-like). Immunophenotyping revealed a pattern of CD33 and/or CD13 positivity, and CD14 and HLA-DR negativity in 96% of cases. CD2 was positive in the FAB variant and in the subtype with basophilic cells, but negative with other subtypes. Three out of five cases with basophilic cell predominance [McKenna et al.: Br J Haematol 50:201, 1982], and one out of two M2-like cases, responded to ATRA therapy. Awareness of the heterogeneity and the atypical morphologic subtypes found in t(15;17) APL will contribute to improved recognition and early institution of ATRA therapy.


Subject(s)
Bone Marrow/pathology , Cytoplasmic Granules/pathology , DNA, Neoplasm/analysis , Leukemia, Promyelocytic, Acute/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Blotting, Southern , Bone Marrow/chemistry , Bone Marrow/immunology , Cell Count , Child , Cytoplasmic Granules/chemistry , Disseminated Intravascular Coagulation/pathology , Female , Histocytochemistry , Humans , Immunophenotyping , In Situ Hybridization, Fluorescence , Karyotyping , Leukemia, Promyelocytic, Acute/classification , Leukemia, Promyelocytic, Acute/genetics , Male , Middle Aged , Polymerase Chain Reaction , Retrospective Studies
4.
Am J Hematol ; 50(3): 209-14, 1995 Nov.
Article in English | MEDLINE | ID: mdl-7485082

ABSTRACT

A case of CD56/NCAM+ malignant lymphoma is reported. Only a rare malignant lymphoma cell showed azurophilic granules in the cytoplasm of Giesma-stained preparations, while electron microscopic examination revealed occasional cytoplasmic granules with paracrystalline inclusions. The most common phenotype seen in NK lymphomas, CD2+, CD3-, CD56+, CD16-, CD57-, was present in the case. Cases with this phenotype have been interpreted to represent either true NK lymphoma or T-cell lymphoma with NK expression. Genotyping, where performed, has shown TCR germline configuration. Our case showed TCR beta rearrangement indicating that the above phenotype can be associated with a peripheral T-cell lymphoma.


Subject(s)
Gene Rearrangement, beta-Chain T-Cell Antigen Receptor , Lymphoma/diagnosis , Aged , CD2 Antigens/analysis , CD3 Complex/analysis , CD56 Antigen/analysis , Humans , Immunophenotyping , Lymphoma/pathology , Lymphoma/therapy , Male , Receptors, Antigen, T-Cell, alpha-beta/genetics
5.
Am J Clin Pathol ; 92(1): 115-9, 1989 Jul.
Article in English | MEDLINE | ID: mdl-2787596

ABSTRACT

The article reports a case of acute T-cell leukemia (T-ALL) with the unusual CD3+, WT31 phenotype. On surface marker analysis, the blast cells were found to be CD7+, CD2-, CD5-, CD1-, CD4-, CD8-, CD3+ and negative for B-lymphoid and myeloid lineage. The cells had both TCR beta and TCR gamma gene rearrangement but had negative results with the monoclonal antibody WT31, which reacts with a framework epitope on the T alpha/beta heterodimer (Ti) of the conventional T-cell receptor (TCR). This suggests an association of the CD3 molecular complex with a different polypeptide (the alternate TCR gamma). In two similar reported cases of T-ALL (WT31-, CD3+, CD4-, CD8-), the CD3 molecular complex was found to be associated with a product of the T gamma gene.


Subject(s)
Antigens, Surface/analysis , Leukemia-Lymphoma, Adult T-Cell/pathology , Antigens, Differentiation, T-Lymphocyte/analysis , Blotting, Southern , DNA Probes , Humans , Infant , Leukemia-Lymphoma, Adult T-Cell/immunology , Male , Phenotype , Receptors, Antigen, T-Cell/analysis
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