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Previous studies of patients with lymphoid malignancies have suggested a relationship between survival and the presence of more than 40% hard-mirror cells in the bone marrow. This report represents the first detailed study of a patient with American Burkitt's lymphoma with numerous hand-mirror cells in the bone marrow during the course of the disease. The Burkitt cells were atypical because of their hand-mirror configuration in the bone marrow, the presence of cytoplasmic glycogen, the finding of an IgG surface marker, and a strongly positive acid phosphatase staining reaction. The presence of increased numbers of hand-mirror forms in the bone marrow during the course of the patient's illness may have clinical significance, because they were replaced by non-hand-mirror Burkitt cells in the terminal phase. More reports and investigations of patients with large numbers of hand-mirror forms in the bone marrow are needed to elucidate the full significance of this unusual cellular phenomenon.

The presence of greater than 3% Sudan black B (SBB) positivity in leukaemic blasts has been considered diagnostic of acute non-lymphocytic leukaemia (ANLL). A rare report has indicated that this finding may not be specific for ANLL. In order to determine whether SBB could be found in acute lymphoblastic leukaemia (ALL) the data on 350 patients with newly diagnosed ALL were reviewed. Six patients (1.6%) were found to have 5% or greater SBB positive blasts. The diagnosis of ALL was supported by morphology, cytochemistries, immunologic markers, therapeutic response, and in one case immunoglobulin gene rearrangement. It is important to recognize the fact that SBB is not specific for AML and may be found in the blasts of patients with ALL.

Acute leukemia associated with the t(4;11)(q21;q23) abnormality demonstrates marked lineage heterogeneity, including cases with features of acute mixed lineage leukemia. We report 7 patients with acute leukemia with the t(4;11) abnormality in which we have defined the range of lineage commitment associated with this disease utilizing a variety of cell characterization techniques. Each case could be classified either as acute lymphoblastic leukemia (ALL) (5 cases) or acute myelogenous leukemia (AML) (2 cases) based on standard light microscopic criteria supplemented by ultrastructural determination of myeloperoxidase. Evidence for acute mixed lineage leukemia was found in one of the AML patients in which coexpression of CD14 and CD19 surface antigens was demonstrated. Overall, the findings further confirm the lineage heterogeneity previously reported in association with t(4;11) acute leukemia. The implications of the findings as to the pathogenesis of t(4;11) acute leukemia are discussed.

The formation of a uropod by lymphocytes (hand-mirror cells) represents a morphologic stage of immune activation and motility in lymphocytes. Immune complexes have been previously shown to induce hand-mirror-cell (HMC) formation in human lymphocytes and have been associated with increased number of HMC in acute leukemia. We studied the ability of immune complexes to induce HMC in patients with Wiskott-Aldrich syndrome (WAS), a disease of cellular immune deficiency. Our findings indicate that lymphocytes from patients with WAS adhere to immune complexes but have a defect in their ability to form HMC when compared with normal human lymphocytes. These results support the concept that immune complexes induce HMC formation and that the HMC is related to the normal cellular immune response.

We describe a patient with chronic myelomonocytic leukemia who showed trisomy 8 in 100% of his bone marrow metaphases. Of interest was the finding that 20% of the Giemsa-banded metaphases also showed t(15;17)(q22;q21), with breakpoints indistinguishable from those seen in cases of acute progranulocytic leukemia (APL). The patient showed no morphologic or clinical evidence of APL, and he died after 6 months, with no evidence that the disease had progressed to acute leukemia. Although cytogenetically the breakpoints appeared to be the same as those in APL, we suspect that this patient's translocation may have differed at the molecular level from the t(15;17) commonly seen in APL.

Terminal deoxynucleotidyl transferase (TdT) is a marker for the diagnosis of acute lymphoblastic leukemia. To determine its value as an indicator of bone marrow remission or impending relapse, serial remission marrows (less than 5% blasts) from 49 patients who had acute lymphoblastic leukemia were examined for TdT by immunofluorescence over the period of a year. Thirty-eight patients (78%) had less than 1% TdT-positive cells. Eleven patients (22%) had slightly elevated levels of TdT (2%-7%) at some time during the study. of these eleven, only two had relapses; however, neither patient had greater than 1% TdT-positive cells within the three months before the relapse. Therefore, it appears that the presence of slightly increased numbers of TdT-positive cells in acute lymphoblastic leukemia remission bone marrows (2%-7%) does not denote impending relapse. In addition, most of the patients with acute lymphoblastic leukemia in remission had less than 1% TdT-positive cells.

This study demonstrates that a differentiation-specific gene, the myeloperoxidase (MPO) gene, is translocated in a patient with acute promyelocytic leukemia (APL). The MPO gene recently has been mapped to chromosome #17, close to the breakpoint involved in the t(15;17) commonly seen in APL. By in situ hybridization, we showed that this gene was translocated from chromosome #17 to #15 in an APL patient. Although the significance of this translocation remains unclear, MPO is known to be highly expressed in APL. The causal relationship between the high expression and translocation of this gene requires further investigation.

Until recently, lineage fidelity was thought to be preserved in leukaemic cells, which by available tests showed surface markers and enzymatic patterns characteristic of an appropriate normal cell lineage and stage of differentiation. Our data indicate that this theory is too restrictive. If leukaemogenesis occurs in pluripotent progenitors in a relatively high percentage of cases, we would propose a model in which lymphoid and myeloid differentiation antigens are expressed simultaneously until the progenitor cell commits to a single lineage. Lineage commitment could involve external factors, e.g. growth factors (Sherr et al, 1985), that cause genes specific for the opposite lineage to be 'switched off'. The control of gene expression in mammalian cells and the specific chromosomal sites of genes coding for the various lineage-associated markers remain uncertain. However, recent studies indicate that most, if not all, leukaemic cells contain chromosomal abnormalities, many involving rearrangements of DNA (Williams et al, 1986). Since the control of eukaryotic gene expression is known to involve numerous sequence elements, some acting at a distance from the site of transcription (Dynan and Tjian, 1985), genetic perturbations within the cell (e.g. a reciprocal translocation) could be expected to deregulate certain genes, leading to their under- or overexpression analogous to activation of the c-myc oncogene by the 8;14 translocation in Burkitt's lymphoma. Thus, an almost infinite variety of cell lineage-related phenotypes could be expected from this mechanism alone, even if the transforming event did not involve a pluripotent stem cell. Also, we have hypothesized that enzymes such as TdT, a DNA polymerase that catalyses polymerization of deoxyribonucleotides without a DNA template, could serve as a modifier of DNA sequences, permitting otherwise inactive genes to be expressed (Stass and Mirro, 1985). It is interesting that most cases of childhood acute mixed-lineage leukaemia are TdT positive, even though this is not true for the chronic leukaemias of adults. It is now clear that unusual combinations of myeloid and lymphoid cell lineages are much more common in acute leukaemia than have been generally recognized or suspected. The traditional division of the acute leukaemias into ALL and AML may not be the most accurate way to represent this class of haematological malignancies. That mixed-lineage leukaemia may require alternative therapy is a clinically important observation and underscores the need for comprehensive testing of blast cells at diagnosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Molecular biologic investigation of the process of immunoglobulin gene rearrangement has elucidated the mechanism of immunologic diversification and has provided essential tools for the study of B-cell neoplasia. The use of immunoglobulin gene probes has permitted a clearer understanding of B-cell malignancies, but has also raised new questions and pointed out new directions for ultimately clarifying the mechanism of B-cell transformation. Thus, we have a difficult challenge ahead, but with our present knowledge, we are in a better position than ever to address critical issues relating to the genesis of lymphoid neoplasia.

From January 1985 to May 1987, we studied 256 adults with newly diagnosed acute leukemia. Acute undifferentiated leukemia (AUL) was diagnosed in 12 of the 256 (4.6%) cases when lineage could not be delineated by light microscopy and light cytochemistry. To further characterize the blasts, immunophenotyping, ultrastructural myeloperoxidase (UMPO), and ultrastructural platelet peroxidase parameters were examined in 10, 11, and 6 of the 12 cases, respectively. Five cases demonstrated UMPO and were reclassified as acute myeloblastic leukemia (AML). Of the six UMPO-negative cases, three had a myeloid and one had a mixed immunophenotype. One UMPO-negative patient with a myeloid immunophenotype was probed for the immunoglobulin heavy chain gene (JH) and the beta chain of the T-cell receptor gene (Tcr beta) with no evidence of rearrangement. Six cases were treated with standard acute lymphoblastic leukemia (ALL) chemotherapy and failed to achieve complete remission (CR). Various AML chemotherapeutic regimens produced CR in only 3 of the 12 cases. One case was treated with gamma interferon and the other 2 with high-dose Ara-C. Our findings indicate a myeloid lineage can be detected by UMPO (5/12) in some cases of AUL. A germline configuration with JH and Tcr beta in one case as well as a myeloid immunophenotype in 3 UMPO-negative cases raises the possibility that myeloid lineage commitment may occur in the absence of myeloid peroxidase (MPO) cytochemical positivity.