Immunological phenotype related to acid alpha-naphthyl acetate esterase and acid phosphatase in childhood acute lymphoblastic leukaemia

In 83 children with acute lymphoblastic leukaemia (ALL) the immunological phenotype of the lymphoblasts was determined using E rosetting, monoclonal anti-T cell sera, surface immunoglobulin staining and common ALL antiserum. The data were compared with acid alpha-naphthyl acetate esterase (ANAE) and acid phosphatase (AP) cytochemical data. The vast majority of T-ALL cells proved to be ANAE-negative (30/31) and AP-positive (29/31). Null-ALL was always AP-negative (12/12), the ANAE reaction was sometimes positive (4/12). In common ALL, findings ranged from negative to positive for both enzymes. Two cases of B-ALL were ANAE-negative and AP-negative. Enzyme cytochemical determinations gave thus preferential patterns, especially for T-ALL and null-ALL. In common ALL, considerable heterogeneity was found, which may be a reflection of differences in maturation between different cases of common ALL.     

Prethymic phenotype and genotype of pre-T (CD7+/ER-)-cell leukemia and its clinical significance within adult acute lymphoblastic leukemia

Pretreatment blast cells from 739 adults with acute lymphoblastic leukemia (ALL) were immunophenotyped as part of a prospective treatment protocol study. Among 192 patients (26%) with T lineage ALL, 47 (6%; 24% of T lineage ALL) had lymphoblasts without sheep erythrocyte rosette formation, but with pan-T antigen CD7 on the membrane and intracellular CD3 proteins mostly in perinuclear accumulation. The T-cell surface antigens CD5 and/or CD2 and focal acid phosphatase were additional markers of this subgroup traditionally called pre-T ALL, whereas thymocyte antigen CD1 as well as CD4 and CD8 antigens were not expressed. Hematopoietic progenitor cell markers, namely terminal deoxynucleotidyl transferase (TdT), and in part common ALL antigen (CD10), HLA-DR antigens, and/or My-10 (CD34), a unique antigen of marrow cells absent in thymus cells, further characterized this immature T-ALL form of putative prothymocytic phenotype (CD7+/intracellular CD3+/TdT+/My-10+/-/HLA-DR+/-/CD10+/-). The prethymic T cell character was supported by germ-line T-cell receptor beta genes found in 21 of 36 patients analyzed. In five cases only T gamma-chain genes were rearranged. Fifteen patients, however, had rearrangements of both T beta and T gamma genes. Immunoglobulin heavy chain genes were rearranged only in two cases. Pre-T ALL differed significantly from E-rosette+ T-ALL in some presenting clinical features, namely mediastinal mass, lymphoadenopathy, and platelet count, and independently of clinical factors in prognosis (P = .02, median remission duration: 15.7 v 33.5 months, and P = .02, median survival time: 24.6 v 50.7 months). We conclude that ALL classification based solely on T- or B-cell lineage affiliation is not sufficient but needs further subdivision according to relevant maturation stages as exemplified here within the T-cell axis. The putative prethymic T cell progenitor phenotype described might help elucidate the sequence of genetic events that commit normal hematopoietic cells to the T-cell lineage.     

Analysis of two new leukemia-associated antigens detected on human T- cell acute lymphoblastic leukemia using monoclonal antibodies

Two monoclonal antibodies (anti-3-3 and anti-3-40) were produced, which identify two new leukemia-associated antigens. Both antibodies reacted with most cell lines derived from patients with T lymphoblastic leukemia (T-ALL), but were not detected on suspensions of normal hematopoietic cells (including thymocytes) by cytotoxicity, absorption, or indirect immunofluorescence assays. Analysis of fresh leukemic cells indicated that anti-3-3 only reacted with T-ALL cells, while anti-3-40 also reacted with some non-T, non-B ALL cells and a few acute myelocytic leukemia (AML) cells. The 3-40 antigen was also found histopathologically in frozen sections of several normal tissues, including the epithelial cells and a few lymphoid cells of the thymus, and some malignant tissues. The 3-3 antigen was not found in any tissue studied. A "double absorption"assay provided additional serologic evidence that the two antibodies identify different antigenic determinants. Biochemical analysis indicated that the molecules immunoprecipitated by anti-3-3 and anti-3-40 have molecular weights of 35,000-40,000 daltons. This study demonstrated that the 3-3 and 3-40 antigens are markers for human T-ALL and can be used along with the normal T-lymphocyte antigen, 3A1, to discriminate T-ALL from cutaneous T-cell lymphoma (CTCL), adult T-cell leukemia (ATL), and T-cell chronic lymphocytic leukemia (T-CLL).     

Receptors for peanut agglutinin (Arachus hypogea) in childhood acute lymphoblastic leukemia: possible clinical significance

The presence of lymphocyte receptors for peanut agglutinin in significant numbers (greater than 15%) was identified on leukemic cells from T-cell acute lymphoblastic leukemia (T-ALL) (3/4), B-cell ALL (B- ALL) (2/4), null cell ALL (8/17), and on normal fetal thymic lymphocytes but not on normal human peripheral blood lymphocytes. Peanut agglutinin (PNA) binding was blocked specifically on leukemia lymphoblasts and thymic lymphocytes by the addition of galactose to the medium. When all immunologic subgroups of ALL are combined, preliminary data suggest that of the 13 ALL patients having greater than 15% PNA- positive lymphoblasts, 8 had relapsed, whereas none of the 12 ALL patients with less than 15% PNA-positive cells have recurrent disease at this time. It is likely that analysis of PNA receptors on ALL lymphoblasts may be a useful adjunct to the existing clinical and immunologic prognostic indicators.     

Cytochemistry and Membrane Markers in Acute Lymphatic Leukaemia (ALL)

136 patients suffering from ALL were subdivided into 5 subtypes (C-ALL, C/T-ALL, pre-T-ALL, B-ALL) according to rosetting tests and using specific antisera directed against membrane antigens. In addition, leukaemic blasts of all patients were investigated according to morphological and cytochemical criteria. In APh and ANAE, indices and the percentages of cases showing a granular staining pattern were high in pre-T- and in T-ALL, but low in C/T- and in C-ALL. PAS-staining, conversely, was more pronounced in C/T- and C-ALL. APh proved to be more discriminative for recognition of the T- and pre-T-ALL subgroups than ANAE, but ANAE-cytochemistry may be useful to detect contaminating normal T-lymphocytes in ALL. Receptors for C₃ were more frequent in C- and in T-ALL than in C/T- and in pre-T-ALL, receptors for F_c were distributed equally among all subtypes. Positivity of C₃- and F_c-receptors was not correlated with cytochemical results. Morphological criteria were not sufficient for subclassification of ALL; the combination of APh- and PAS-staining, however, is valuable to differentiate between C-subgroups and T-subgroups.     

Chromosome Studies in Acute Lymphoblastic Leukaemia (ALL)

Chromosome banding studies of the bone marrow were performed in 35 adult (> 14 years) patients with acute lymphoblastic leukaemia (ALL). Surface marker analysis was done in 24 of these and revealed 4 B-ALL, 5 T-ALL and 15 non-T non-B ALL. Most patients were studied at diagnosis before any treatment. A clonal karyotypic abnormality was found in 16 patients (46 %) initially. A Philadelphia chromosome was found in 3 patients, all belonging to the non-T non-B group. 5 patients, who all had blast cells with morphologic characteristics of Burkitt type L₃, were found to have bone marrow cells with a 14q+ marker chromosome. In at least 4 cases this was due to a t(8;14). The cytogenetic findings showed some correlation to the ALL subgroup, but not to the response to treatment or the prognosis.     

Analysis of human myelogenous leukemia cells in the fluorescence- activated cell sorter using a tumor-specific antiserum

The properties of a rabbit antiserum (anti-AML) raised to a purified protein from membranes of human acute myelogenous leukemia (AML) cells is described. Bone marrow and peripheral blood leukocytes (PBL) from either normal individuals or patients with either myeloproliferative or other disorders were analyzed in a fluorescence-activated cell sorter (FACS IV) after labeling with anti-AML, normal rabbit serum (NRS), or antiserum raised to normal human membrane antigens. Of 40 cell samples from patients with acute myelogenous leukemia, 39 reacted strongly with the anti-AML antiserum. Similarly, all of 19 specimens from patients with chronic granulocytic leukemia reacted with the anti-AML. When 42 bone marrow or PBL samples from patients with a variety of lymphoproliferative disorders were examined, 2 specimens reacted with the antiserum, both from individuals with diagnoses of acute lymphocytic leukemia (ALL). None of the 14 normal bone marrow or PBL donor specimens tested reacted with the antiserum. It was also found that essentially all samples from patients in clinical remission from AML had high numbers of cells reactive with the anti-AML. When cells from such individuals were labeled and sorted on the FACS IV, it was found that cells fluorescing strongly with the anti-AML contained cells of both myeloid and lymphoid origin. The implications of these results are discussed.     

Absence of terminal transferase may predict failure of remission induction in childhood ALL

Two children with acute lymphoblastic leukemia (ALL), whose lymphoblasts lacked terminal deoxynucleotidyl transferase (TdT) by both enzyme and fluorescent antibody assay, responded poorly or not at all to vincristine and prednisone. Both patients had high presenting white counts and mixed L1-L2 morphology. Lymphoblasts from one patient, an adolescent boy with a mediastinal mass, possessed surface membrane receptors for sheep red cells (E) and for complement (EAC) and had elevated adenosine deaminase activity (ADA). Lymphoblasts from a 2.5-yr- old boy without a mediastinal mass did not form E or EAC rosettes and did not express the la-like antigen or carry surface immunoglobulin. The poor response to therapy and absence of TdT were associated with a lymphoblast phenotype suggestive of a highly differentiated T-cell- derived line in one instance and an undifferentiated cell in the other instance. It is postulated that absence of TdT may predict poor therapeutic efficacy of vincristine and prednisone in acute lymphoblastic leukemia in childhood. The absence of TdT may correlate with other developmental characteristics of lymphoblasts, such as altered function or low numbers of glucocorticoid receptors or resistance to lysis by steroid drugs. Determination of many parameters of lymphoblast phenotype at diagnosis to characterize the nature of the malignant cells more precisely may ultimately enhance our understanding of, and improve therapy for, the group of leukemic children who fail to respond to standard regimens.     

Change in Cellular Phenotype from Lymphoid to Erythroid in a Case of ALL

Acute leukaemia was diagnosed in a 3-month-old boy. Initial blood leucocyte count was 97 × 10⁹/1, 92% of the cells were morphologically small lymphoblasts which according to surface marker analysis were of the common ALL (non-T non-B) type. Remission was achieved with initial treatment. During relapse 5 months later a morphologically different leukaemic cell appeared in the bone marrow, blood and liquor. This cell type which dominated during the terminal stage of the disease was larger and had an abundant bosophilic cytoplasm which contained PAS-positive granulae. Sudan, myeloperoxidase and benzidine staining gave negative results. Neither T nor B lymphocyte markers were seen but a strong surface expression of glycophorin A was found by indirect immunofluorescence with specific rabbit anti-glycophorin A antiserum. The cells showed a unique surface glycoprotein pattern. Bone marrow karyotype analysis gave in about 80%: 47,XY, + 8,t(4:11) indicating that this blast cell represented a malignant clone. As glycophorin A is expressed exclusively on erythroid cells and their precursors, this finding indicates a change from a ‘lymphoid’ to an erythroid phenotype of the leukaemic cells during the course of the disease.     

Acute lymphoblastic leukemia and non-Hodgkin's lymphoma of T lineage: colony-forming cells retain growth factor (interleukin 2) dependence

The regulatory role of interleukin 2 (IL 2) in the proliferation of T acute lymphoblastic leukemia (T-ALL) and T non-Hodgkin's lymphoma (T- NHL) cells from six individual patients was analyzed in a colony culture system to which pure recombinant IL 2, and the lectin phytohemagglutinin (PHA) or the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA), had been added. The proliferative response was correlated with the inducibility of receptors for IL 2 on the surface membrane of T-ALL and T-NHL cells by incubation with TPA or PHA for 18 hours. Leukemic T cell colonies, identified by immunophenotyping or cytogenetic analysis, appeared in vitro following TPA and IL 2 stimulation in all six cases. Accordingly, receptors for IL 2, initially absent from the cell surface, were found on high proportions of the T-ALL and T-NHL cells after in vitro exposure to TPA. In contrast, colony formation stimulated by PHA and the induction of IL 2 receptors by PHA were limited to the one case of T-NHL with the mature thymocyte immunophenotype. The cells from the other patients, expressing common or prothymocyte phenotypes, did not respond to PHA. No colonies were formed in any of these cases when PHA or TPA was withheld from the IL 2-containing cultures. Although colony growth depended absolutely on exogenous IL 2 in three cases (ALL), in the three other cases (one ALL, two NHL) some colonies grew also when no IL 2 had been added to the cultures. Upon further analysis of the cells of one of the latter patients, it was found that the cells produced IL 2 and proliferated in response to this endogenous IL 2. The results from this study indicate that the requirements of endogenous v exogenous IL 2 for cell proliferation in T-ALL and T-NHL and IL 2 receptor activation by PHA and TPA vary from patient to patient. In addition, they support the notion that T-ALL and T-NHL cells have not lost dependence on IL 2 and IL 2 receptor activation for in vitro growth.     

Distinct human leukemia-associated cell surface glycoprotein GP160 defined by monoclonal antibody SN6.

In this study, a monoclonal antibody (mAb) termed SN6 was generated by immunizing a mouse with a non-T-cell leukemia antigen preparation isolated from cell membranes of leukemia cells derived from a patient (FJ) with non-T/non-B-cell-type acute lymphoblastic leukemia (ALL). SN6 was tested against a variety of cultured and uncultured human cell specimens by using a sensitive cellular radioimmunoassay. Among the 26 cultured malignant and nonmalignant cell lines tested, SN6 reacted with all of the 6 leukemic non-T/non-B (including pre-B)-cell lines tested--i.e., KM-3, NALM-16, REH, NALL-1, NALM-1, and NALM-6. Of these cell lines, 5 were derived from individual patients with ALL; the remaining 1 was from a patient with chronic myelocytic leukemia in blast crisis. In addition, SN6 reacted with 3 of 3 leukemic myelo-monocytic cell lines tested--i.e., ML-2, HL-60, and U937. SN6 did not react with any other cell lines. A consistent result was obtained with 42 fresh (uncultured) cell specimens derived from individual patients with several different types of leukemias. SN6 reacted with 11 of 16 non-T/non-B (including pre-B)-cell ALL specimens. In addition, it reacted with various myelo-monocytic leukemia cell specimens to various degrees. SN6 did not show a significant reaction with normal peripheral blood cells tested, which included B cells, T cells, granulocytes, monocytes, and erythrocytes. However, it reacted with a small population (approximately 1% as determined by immunofluorescence staining) of normal bone marrow cells. The approximate molecular mass of the glycoprotein antigen defined by SN6 was determined to be 160,000 by radioimmunoprecipitation followed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Only one component of 80,000 daltons was formed upon reduction of the 160,000 molecular mass antigen. Therefore, this antigen is apparently a homodimer of a 80,000-dalton subunit. This conclusion was further corroborated by two-dimensional gel analysis, which showed a single well-defined spot for the reduced antigen. We designate this distinct human leukemia-associated cell surface antigen "GP160."     

Monoclonal antibody that defines a unique human T-cell leukemia antigen

We have generated and characterized a hybridoma monoclonal antibody, termed SN1, that defines a unique human T-cell leukemia antigen. This antibody was generated by using a human leukemia antigen preparation isolated from cell membranes of MOLT-4, a leukemia T-cell line derived from a patient with T-cell-type acute lymphoblastic leukemia (T-ALL). SN1 was characterized by a sensitive microscale radioimmunoassay using a variety of cultured and uncultured human cells. In selected cases, the cell specimens were further tested by immunoperoxidase staining and an immunofluorescence staining test. The results of the radioimmunoassay were in agreement with those of the two other tests. Among the various cultured malignant and nonmalignant cell lines, SN1 reacted only with leukemia T-cell lines derived from patients with T-ALL; it reacted with all six T-ALL cell lines tested-i.e., JM, CCRF-CEM, CCRF-H-SB2, RPMI 8402, PEER, and MOLT-4. In the case of uncultured cell specimens derived from cancer patients, SN1 reacted with four of four cases of T-ALL but did not react with specimens derived from 41 patients with other types of cancer. SN1 did not react with any normal human cell specimens tested, both cultured and uncultured. These specimens include normal lymphoblastoid cell lines, thymocytes, bone marrow cells, spleen cells, lymph node cells, peripheral blood mononuclear cells, lymphocytes containing B and T cells, purified T cells, monocytes, granulocytes, erythrocytes, and platelets. Furthermore, SN1 did not react with phytohemagglutinin-activated T cells nor with concanavalin A-activated T cells. The results show that monoclonal antibody SN1 defines a type of human leukemia antigen that is expressed on the cell surface of T-cell-type ALL cells. The results further show the usefulness of SN1 in the diagnosis of cancer patients and suggest its therapeutic potential. We designate this antigen TALLA, a T-cell ALL antigen.     

Phenotypic analysis of acute lymphoblastic leukemia (ALL) cells which are classified as non-T non-B and negative for common ALL antigen

When phenotypic marker analysis of acute lymphoblastic leukemia (ALL) cells (102 cases) was performed, a group of ALL cells (15 cases) classified as non-T non-B, and negative for common-ALL antigen (CALLA) was characterized in a focused manner. "Non-T non-B" was defined as negative for T cell properties such as E-rosetting or reactivity with anti-human T-cell monoclonal antibodies (T101, WT1), and absence of any B-cell characteristics (cell surface and/or cytoplasmic immunoglobulin and reactivity with B1 monoclonal antibody). Despite their marked heterogeneity, CALLA(-) non-T non-B ALL cells revealed three different phenotypic patterns in terms of presence of terminal deoxynucleotidyl transferase (TdT) and of reactivity with antimyeloid (MCS1) or myelomonocyte (MCS2 and OKM1) monoclonal antibodies. Four of 15 cases reacted with some myeloid-specific antibodies, but were negative for TdT. Six cases had both MCS2 antigen and TdT. The remaining five cases expressed no myeloid antigens, but were positive for TdT with some exceptions. These findings showed that acute leukemias with myeloid antigens might be involved in CALLA(-) non-T non-B ALL having no relationship to the presence of TdT, and, furthermore, that the blasts with simultaneous expression of TdT and myeloid-specific antigen (MCS2) might represent an immature stage in hematopoietic differentiation closely corresponding with the bifurcation of the lymphocyte/myeloid pathway. Alternatively, only five cases remained "unclassified leukemia." We therefore think that the detailed examination of CALLA(-) non-T non-B ALL cells using myeloid specific antibodies is helpful in clarifying the characteristics of myeloid precursors and the common bipotential stem cell of lymphoid and myeloid progenitors.     

Relationship of a leukemia-associated antigen to the presence of lymphoblasts in the peripheral blood in children with acute lymphocytic leukemia

Peripheral blood samples from 57 children with newly diagnosed E- rosette-negative, surface-immunoglobulin negative acute lymphocytic leukemia (ALL) were studied for the presence of a leukemia-associated antigen (ALLA). Ficoll-Hypaque separated cells were tested using a rabbit antiserum to human null lymphoblasts and an indirect immunofluorescent assay. The percentage of ALLA-positive cells were compared to the percentage of lymphoblasts determined by differential counts of a Wright-Giemsa-stained smear of a concurrently obtained peripheral blood sample. The mean ratio of percentage of lymphoblasts to percentage of ALLA-positive cells was 0.90. However, in 13 patients, the ratio of percent of ALLA-positive cells to percent of lymphoblasts was equal to or greater than 2:1. In the blood of 6 additional children (5 newly diagnosed, 1 relapsed patient) in whom no morphologically identifiable lymphoblasts were detected. ALLA-positive cells were present (7%-49%). These results indicate that testing for ALLA-positive cells in a sensitive technique for detection of leukemic cells in children with ALLA-positive ALL.     

Expression of common acute lymphoblastic leukemia antigen (CALLA) by lymphomas of B-cell and T-cell lineage

Previous studies have demonstrated that the common acute lymphoblastic leukemia antigen (CALLA) is expressed by leukemic cells from approximately 80% of patients with non-T-cell ALL and 30%-50% of patients with chronic myelocytic leukemia in blast crisis. A small number of normal bone marrow and fetal liver cells also express CALLA, but the functional role of this molecule is unknown. In the present study, we have used a monoclonal antibody (J5) specific for CALLA to study the expression of this antigen in non-Hodgkin's lymphomas. Within the B-cell lymphomas, it was found the CALLA was expressed by almost all Burkitt's and nodular poorly differentiated lymphocytic lymphomas. Within the T-cell lymphomas, CALLA was expressed in 40% of patients with lymphoblastic lymphoma. Three of 3 Burkitt's lymphoma cell lines and three of eight T-lymphoblast cell lines were also found to express CALLA. Normal spleen, lymph node, and thymus cells were not reactive with J5 antibody. These findings indicate that expression of CALLA is not limited to relatively undifferentiated leukemic lymphoblasts but also occurs in more differentiated lymphoid malignancies. However, normal differentiated lymphoid cells in lymph node, spleen, and thymus, which have a phenotype similar to that of lymphoma cells, do not appear to express CALLA.     

髓系抗原、P-糖蛋白和CD34抗原在急性淋巴细胞白血病中的表达及其意义

目的　探讨急性淋巴细胞白血病 (ALL)的髓系抗原、P 糖蛋白 (P gp)和CD3 4 表达特点及其与预后的关系。方法　采用间接免疫荧光法标记流式细胞仪 (FCM )检测 84例初治ALL患者的免疫表型。结果　ALL髓系抗原阳性率为 17.8% ,其中CD13 阳性最常见。CD3 4 表达阳性率为45 .3 % ,与髓系抗原表达和治疗缓解率无显著相关性。髓系抗原阳性组病例 (My ALL)肝脾肿大明显 ,白细胞总数增高显著 ,完全缓解 (CR)率明显低于阴性组病例 (P <0 .0 1)。P gp阳性表达率为 3 2 .1% ,P gp表达阳性与My ALL化疗效果有相关性。结论　My ALL细胞对于常规诱导缓解方案不敏感 ,选择兼顾ALL AML的方案可提高治疗效果。P gp高度表达与低CR率有密切关系     

A Hodgkin cell-specific antigen is expressed on a subset of auto- and alloactivated T (helper) lymphoblasts

A Hodgkin cell-specific antigen detected by the monoclonal antibody Ki- 1 was found on T helper lymphocytes after activation by autologous and allogeneic stimulator cells. About 50% of lymphoblasts generated by auto- and alloactivation reacted with the antibody. In contrast, only less than 6% of lymphoblasts stimulated with Con-A, phytohemagglutinin (PHA), or protein A, and none of lymphoblasts activated by oxidative mitogenesis, expressed this antigen. Among several permanent cell lines tested, the K562, MOLT-4, HL-60, and EBV transformed B lymphoblastoid cells reacted with the Ki-1 antibody. The results may indicate possible relationships between the autoreactive subset of T lymphocytes and the pathogenesis of Hodgkin's disease.     

Prognostification of ALL by Cytogenetics

Cytogenetic abnormalities in chromosomal number and structure are common in pediatric ALL and some have prognostic significance. One interesting association between cytogenetic status and treatment response involves the metabolism of methotrexate. Hyperdiploid lymphoblasts accumulate increased amounts of MTX and MTX polyglutamates, and they have higher basal apoptotic rates compared with leukemic cells with lower ploidy and normal cells. These characteristics may contribute to the better outcomes observed for patients with hyperdiploid lymphoblasts. A number of recurrent chromosomal abnormalities have been shown to have prognostic significance, especially in B-precursor ALL. Some chromosomal abnormalities are associated with more favorable outcomes, such as high hyperdiploidy (51–65 chromosomes) and the ETV6–RUNX1 fusion. Others are associated with a poorer prognosis, including the Philadelphia chromosome [t(9;22)], rearrangements of the MLL gene (chromosome 11q23), and intrachromosomal amplification of the AML1 gene (iAMP21).     

Immunologically Defined Subclasses of Acute Lymphoblastic Leukaemia in Children: their Relationship to Presentation Features and Prognosis

S ummary. Leukaemic cells from 542 patients under 21 years of age with a diagnosis of acute lymphoblastic leukaemia (ALL) were typed with immunological cell surface markers between June 1975 and December 1979; 379 of these patients entered into the trials up until December 1978 have been followed for more than 1 year. They were divided into four subgroups: common (c) ALL, T (thymic) ALL, 'null' (or 'unclassified') ALL and a rare lymphoma/leukaemia type B-ALL. A T-cell phenotype was found more frequently in boys and was usually but not invariably associated with a high white cell count at presentation. A mediastinal thymic mass was present in 53% of T-ALL patients but was not observed in any unequivocal non-T ALL. Clinical prognosis differed substantially between the three major phenotypic classes, remission induction rate and remission duration being lowest in T-ALL, better in 'null' ALL, and highest in cALL ( P trend < 0·0001; P =0·0002 for comparison of cALL versus T-ALL). There was a much higher incidence of CNS involvement in the T-ALL group than in the cALL group or 'null' ALL group and although this was strongly correlated with WBC count it was also significantly associated with T-ALL independent of WBC count.
Overall in this series and also within the major cALL subclass there is a strong correlation between high WBC count and poor clinical response (remission induction and duration). When the three major immunological subclasses are adjusted for WBC count the prognostic correlation of antigenic phenotype is reduced and statistically insignificant.
It is suggested that immunological (and enzymatic) phenotype of ALL subclasses may not be an independent correlate of prognosis but nevertheless is linked to other cell differentiation features, especially growth rate and sites of clonal expansion (e.g. marrow versus thymus), which critically influence the size of the clonogenic     

A monoclonal antibody (WT1) for detecting leukemias of T-cell precursors (T-ALL)

The selectivity of a monoclonal anti-T antibody, designated WT1, has been assessed in a series of 906 leukemias and lymphomas. In acute lymphoblastic leukemias, WT1 reacts comprehensively and selectively with thymic acute lymphoblastic leukemia (ALL) cells in untreated or relapsed patients, thus overriding the extensive antigenic diversity of this cancer and the immaturity of the cell type involved. All 80 cases of thymic ALL examined were WT1-positive. In addition, 18 cases of presumptive prethymic ALL were also WT1-positive, but were unreactive with other maturation-linked T-cell markers. The phenotype WT1+ HLA-DR TdT+ appears to be unique to T-ALL and can therefore be used systematically for the differential diagnosis of this poor prognosis subtype of ALL. Virtually all ALL cases can now be placed into one of two major subgroups representing transformed precursors of either the T- or B-cell lineage. WT1 identifies a single polypeptide of approximately 40,000 mol wt and is similar to two previously described monoclonal antibodies.