Lack of correlation between immunoglobulin and T cell receptor gene rearrangements and TdT expression in acute myeloid leukaemia.

Thirty-two cases of acute myeloid leukaemia (AML) were examined for expression of terminal deoxynucleotidyl transferase (TdT) and rearrangements of the genes coding for the immunoglobulin heavy chain and the beta chain of the T cell receptor, in order to establish whether these two forms of lineage infidelity are linked. In 17 cases of AML with greater than or equal to 10% TdT+ cells, three cases showed evidence of gene rearrangement, two having clonal rearrangements in the immunoglobulin gene and one with a rearranged T cell receptor gene. Among 15 AML cases without significant numbers of TdT-positive blasts, three cases had rearrangements in both immunoglobulin and T cell receptor genes, while a fourth case had an immunoglobulin gene rearrangement. No relationship was seen between lymphoid gene rearrangements and expression of the lymphoid surface antigens CD7 and CD10. The lack of association between TdT expression and gene rearrangements does not support the concept of an orderly activation of the recombinase machinery in those cases of AML with features of early lymphoid differentiation.     

Therapeutic and prognostic implications of glucocorticoid receptors and terminal deoxynucleotidyl transferase in acute leukemia

Glucocorticoid receptors (GR) have been reported to predict clinical responsiveness to glucocorticoid therapy and to possess prognostic significance in leukemia. A raised level in terminal deoxynucleotidyl transferase (TdT) also seems to suggest clinical responsiveness to prednisone and vincristine therapy. We have investigated these two biochemical markers in the leukemic blasts in 23 patients with acute myeloid leukemia (AML) and in 19 patients with acute lymphoblastic leukemia (ALL) and have compared the binding data with clinical glucocorticoid sensitivity. with response to chemotherapy, with survival and with TdT. In 25 of these patients we have also investigated the in vitro glucocorticoid sensitivity by measuring dexamethasone inhibition of radiolabelled uridine and thymidine incorporation into the leukemic blasts.In patients with AML. GR levels were mostly high but did not correlate with the in vitro sensitivity. response to chemotherapy or survival. On the other hand, in the 19 patients with ALL there seemed to be a correlation between GR and in vitro sensitivity and between GR and clinical responsiveness to glucocorticoid therapy. Furthermore, patients with low levels of either TdT or GR seemed to be associated with poor prognosis. TdT activity and GR, however, did not associate with one another.TdT is a useful marker for the identification of lymphoblasts but, by itself, is not connected with glucocorticoid sensitivity. GR, when applied to ALL. could supplement TdT determination by predicting response to therapy.     

Terminal deoxynucleotidyl transferase and CD7 expression in acute myeloid leukemias are not associated with a high frequency of immunoglobulin and/or T cell receptor gene rearrangement.

Within normal hemopoiesis, the intranuclear DNA polymerase TdT seems to be exclusively expressed by T and B lymphoid precursor cells. Double staining experiments showed that TdT can also be expressed in blast cells of certain acute myeloid leukemias. Recent reports described a very strong association between TdT expression and rearrangements of IgH and TcR genes in such AML specimens, suggesting a predominant lymphoid commitment of these TdT positive AML blasts. When submitting 24 serologically and morphologically well-characterized TdT positive AML specimens for additional genotypic analysis to determine the IgH and TcR gene configuration, we observed that only four had clonally rearranged IgH and/or TcR genes, whereas 20 had germ line configuration. This frequency is clearly lower than previously reported and not necessarily different from rearrangement frequencies reported for TdT negative AML (4-40%). It would seem to us, therefore, that the expression of TdT in otherwise well-defined AML blasts is not necessarily associated with a higher frequency of immunoglobulin and/or T cell receptor gene rearrangement.     

Epidermal growth factor receptor expression in acute myelogenous leukaemia is associated with clinical prognosis

The epidermal growth factor receptor (EGFR) family belongs to type I receptor tyrosine kinases. Overexpression or mutation of EGFR/ErbB1 gene has been detected in a large number of human solid tumours. According to some previous report, this gene is not expressed in hematological malignancies. However, two recent clinical case reports showed that erlotinib caused complete remission of acute myeloid leukaemia (AML)-M1 in patients who had both AML-M1 and non-small-cell lung cancer. These results are supported by preclinical studies in which EGFR tyrosine kinase inhibitors have anti-proliferative effects on AML. These findings prompted us to determine whether EGFR is expressed in human AML, through a large-scale screening of both leukaemic cell lines and clinical samples. Our results show that EGFR is expressed by about 33% of human AML (containing M1 to M7 subtypes) and by some human leukaemia cell lines (K562, MEG-01, CEM and SKO-007). Its expression is not limited to certain AML types but has been detected in many leukaemic cells. In addition, EGFR expression was intimately associated with the poor clinical outcomes. Finally, we find that only EGFR-positive leukaemic cells respond to antibody-dependent cellular cytotoxicity of cetuximab, the monoclonal antibodies against EGFR.     

Terminal deoxynucleotidyl transferase activity and blast cell characteristics in adult acute leukemias

Terminal deoxynucleotidyl transferase (TdT) measurements in patients with leukemias and other hematopoietic disorders were correlated with cell surface phenotypes and hematological and cytochemical characteristics.High TdT activity was found in thymus and in all T-and non-T/non-BALL patients in active phase. Low TdT activity (< 2 U/mg DNA) was found in blood or bone marrow from normal persons. ALL patients in remission, immunologically characterized T-cell disorders (T-cell CLL, Sezary syndrome, mycosis fungoides and infectious mononucleosis). B-cell ALL, most AML and other hematopoietic disorders. DNA polymerase activity was high in immature cells when compared to mature leukocytes. About $\text{1}\text{3}$ of AML patients which had high TdT activity were indistinguishable from other AML patients on the basis of blast cell characteristics. Two patients at initial diagnosis had the morphological and cytochemical characteristics of lymphoblasts and high TdT activity, but on relapse, the blasts had the typical characteristics of myeloblasts and low TdT activity.Among 10 patients with Ph¹ chromosome positive acute leukemia $\text{4}\text{5}$ patients with lymphoid-appearing blasts and $\text{2}\text{5}$ patients with myeloid-appearing blasts had high-TdT activity.The results of this study show that although about $\text{1}\text{3}$ of AML patients may have high TdT activity, it is still a useful marker for the diagnosis of ALL. In addition, Ph¹ chromosome positive acute leukemia may represent a distinct entity although related in its origin to both non-T/non-B ALL and blastic phase of CML.     

DNA ligases in human leukemia

Following partial purification on sucrose gradient and/or phosphocellulose chromatography, DNA ligase was tested in peripheral white blood and bone marrow cells of nearly 100 patients with various kinds of leukemias, mainly acute leukemias. Terminal deoxynucleotidyl transferase (TdT) was tested in parallel. DNA ligase of acute myeloblastic leukemia (AML) was extracted with the same sedimentation coefficient (5.5S) on sucrose gradient, and eluted with the same KCl molarity (0.3 M) than the one extracted from normal lymphocytes. Acute lymphoblastic leukemias (ALL) were characterized by no detectable DNA ligase activity--in most T or non T-non B-ALL, or a low activity in pre-B and B (Burkitt type) ALL, with levels similar to the one observed in chronic lymphocytic leukemia (CLL). An inverse relationship was observed between DNA-ligase and TdT in ALL, ligase being undetectable in cells positive for TdT and being present in some T or non T-non B, and in all pre-B and B-ALL negative for TdT. AML and chronic myelocytic leukemia (CML) were characterized by a markedly higher DNA-ligase activity. This activity was higher in the most differentiated subtypes--M2, M3 and M4 subtypes of FAB classification--and in CML. Moreover a high degree of correlation was observed in AML between the DNA ligase activity and the S phase fraction measured by 3 H-thymidine autoradiography or flow cytophotometry on the total cell sampling. Besides their clinical interest, these results are discussed in relation with the role of DNA-ligase in DNA replication and repair.     

High terminal deoxynucleotidyl transferase activity in pediatric patients with acute lymphocytic and acute myelocytic leukemias.

Specificity of TdT5 as a marker for ALL was evaluated by determining its activity in cells from normal control subjects and from 35 pediatric patients with ALL, AML, Hodgkin's disease and disseminated Burkitt's lymphoma. We evaluated the DNA polymerase activity, cell surface phenotypes (E rosettes, EAC rosettes, Smlg and la-like, HTLA and cALL antigens), and hematological and cytochemical characteristics in both the normal and patient groups. DNA polymerase alpha + beta and DNA polymerase gamma activity were indiscriminately high in all immature cells as found in ALL, AML, Burkitt's lymphoma and phytohemagglutinin-stimulated normal lymphocytes, when compared to mature leukocytes found in normal individuals or in patients whose cancer was in remission. High TdT activity was found in 24 of 26 T and non-T/non-B ALL patients in active phase as well as in two of three AML patients one of whom had Auer rods. Thus, TdT, although valuable for monitoring ALL patients, may have limitations in separating AML from ALL.     

Terminal transferase levels in chronic myelogenous leukemia in blast crisis and in remission

Terminal deoxynucleotidyl transferase (TdT) has been cited as a possible biological marker for acute lymphoblastic leukemia (ALL) and the blast phase of chronic myeloid leukemia (CML). In the present study high levels of TdT, comparable to levels present in normal thymus, were observed in circulating leukocytes of a CML patient in blast crisis. Sequential studies revealed disappearance of TdT from circulating leukocytes after remission was induced with vincristine and prednisone therapy. Blood TdT returned to moderately elevated levels in the absence of detectable circulating blasts, 5 months before the reappearance of blast crisis. During blast crisis the malignant cells were devoid of myeloid features on light and electron microscopy and were peroxidase negative and periodic acid-Schiff (PAS) positive. These studies demonstrate that elevated TdT levels may occur with or without detectable morphologic evidence of circulating blast cells. The presence of complement receptors on agranular blasts during the blast phase of chronic myeloid leukemia is a new finding.     

Ph1-positive acute myelocytic leukemia with high TdT levels

The authors have determined TdT levels in a case of Ph1-positive AML. Peripheral blood cells and bone marrow cells taken during the various phases of the disease were examined. Liquor cells were analyzed when symptomatic central nervous system involvement occurred. High TdT levels were found in all of the phases of the disease including the liquor. TdT eluted at various isoelectric points indicating a shifting of the activity to greater molarity during progress of the disease. Two different forms of TdT were present in the liquor. The authors speculate about the existence of a relation between TdT levels and Ph1-positive leukemia. They point out the importance of TdT levels as functional criterion of remission in acute leukemia. Finally, the existence of different forms of TdT could be the expression of a clonal selection caused by therapy or of a spontaneous clonal competition.     

Terminal transferase positive acute myeloid leukemia: immunophenotypic characterization and response to induction therapy

A quantitative evaluation of terminal deoxynucleotidyl transferase (TdT) was performed using a highly sensitive enzyme immunoassay (EIA) in 72 previously untreated patients with acute myeloid leukemia (AML). Biological analysis of the leukemic cells included in all cases cytochemistry, search for Ph' chromosome and immunophenotyping with both anti-lymphoid and anti-myeloid monoclonal antibodies (MoAbs). Thirteen AML cases (18 per cent) were considered TdT+ by EIA. According to the FAB classification, almost all of them (12 out of 13) were within the M1 and M2 subgroups. A mixed lymphoid-myeloid phenotype was observed in one of the 13 TdT+ cases, while in none of the others were lymphoid features detected. Nine of the 10 EIA TdT+ cases studied in parallel were TdT positive with the conventional immunofluorescence assay. All patients received standard protocol chemotherapy and in 61 (13 TdT+, 48 TdT--) the response to induction treatment was analysable. Only 3/13 TdT+ patients (23 per cent) achieved a complete remission (CR), while in the TdT- group 38 patients had a CR (79 per cent) and 10 were resistant (p less than 0.01). It is suggested that the incidence, biological interest and prognostic significance of TdT+ AML should encourage the routine and more accurate search for this marker in all patients with AML.     

Rearrangement of immunoglobulin and T cell antigen receptor genes in acute myeloid leukemia with lymphoid-associated markers

Ten cases of adult acute myeloid leukemia (AML) displaying lymphoid-associated markers CD7 and/or terminal deoxynucleotidyl transferase (TdT) have been investigated for rearrangement of immunoglobulin and T cell antigen receptor beta and gamma genes. Two of six TdT+ cases had clonally rearranged Ig genes, whereas six of eight CD7+ AMLs, including three that were TdT+, had a germ line configuration of both immunoglobulin and T cell receptor beta and gamma genes. A single case of CD7+ TdT- AML had clonal rearrangement of all three genes. These results indicate that expression of TdT and/or CD7 is not accompanied by gene rearrangement in most cases of adult AML. A minority of cases, displaying lymphoid-associated phenotypic markers and accompanying gene rearrangement, may represent a distinct subgroup of AML that arises from a rare, primitive stem cell, possessing extensive multilineage potential.     

TCRδ Gene Rearrangements in Acute Myeloid Leukemia with T-lymphoid Antigen Expression

In this review we present our data concerning T-cell receptor (TCR) δ gene rearrangements in acute myeloid leukemia with cuexpression of T-lymphoid features (CD2/CD4/CD7; Ly+ AML). We found a correlation between TCRδ gene rearrangements and coexpression of these T-lymphoid features. Ten of 66 Ly+ AML and only one of 44 AML cases without this coexpression exhibited TCRδ gene rearrangements (p = .028). In contrast, no correlation was observed between terminal deoxynucleotidyl transferase (TdT) expression and the occurence of TCRδ gene rearrangements in AML. Rearrangements were found in two of 25 AML with and seven of 71 AML cases without TdT expression. Interestingly, nucleotide sequencing of junctional sites revealed up to 36 N-nucleotides in cases without or with only weak TdT expression indicating downregulation of TdT expression after the TCR rearrangement took place. Complete Vδ1Jδ1 and incomplete Dδ2Jδ1 gene rearrangements were observed most frequently in Ly+ AML. These recombination patterns were similar to patterns observed in acute T-lymphoblastic leukemia with coexpression of myeloid features (My+ T-ALL) suggesting transformation of a common myeloid/T-lymphoid progenitor cell in these cases.     

Cell-cycle prognostic value in adult acute myeloid leukemia. The choice of the best variables

Flow cytometry with simultaneous analysis of DNA and protein content allows a most exhaustive study of cell-cycle for the prognostic evaluation of acute myeloid leukemia (AML). Sixty-seven cases of AML were studied before any form of chemotherapy had been undertaken. We determined the following cell-cycle variables: S, S + G2 + M, low protein content fraction (LPC-fraction) and high protein content fraction of G1 (HPC-G1). Patients were stratified according to age: S and S + G2 + M phases were higher for patients over 50 who did not achieve a complete remission. LPC-fraction was significantly lower for patients older than 50 who did not achieve a complete remission not only compared to the complete remission group of patients over 50, but also compared to the younger non responder group. The duration of survival was significantly longer when LPC-fraction was higher than 26% and HPC-G1 lower than 70%. Length of survival was also better when S + G2 + M was longer than 5.75%. Analysis of the therapy failure showed that S + G2 + M and LPC-fraction were significantly different between the complete remission group and the group of patients dying in aplasia. Overall, patients older than 50 with a proliferative leukemia had a worse prognosis.     

DNA aneuploidies in adult patients with acute myeloid leukemia. Incidence and relation to patient characteristics and morphologic subtypes

Analyses of the cellular DNA content were carried out by flow cytometry (FCM) in 148 adult patients with acute myeloid leukemia (AML) to assess the incidence of DNA aneuploidies and its relation to patient characteristics and morphologic subtypes. DNA aneuploidies were found in 54 of 131 patients with de novo AML (41.2%) and in 4 of 17 patients with AML after preleukemic syndromes. Subclassification according to morphology revealed the lowest rate of DNA aneuploidies in M1 leukemias (25%) and a significantly lower degree of DNA aneuploidy in M1 and M2 cases as compared to M4 and M5 subtypes (P less than 0.05). Within the group of M4 and M5 leukemias, patients less than or equal to 40 years of age had a higher frequency of aneuploid DNA stemlines (71.4%) than older patients (33.3%) (P less than 0.025). No differences between patients with and without DNA aneuploidy were identified for the initial leukocyte count, serum LDH, bone marrow S-phase index, bone marrow cell count/mm3 bone marrow nor the initial response to the induction regimen of 6-thioguanine, cytosine arabinoside, and daunorubicin (TAD). For remission duration a tendency towards a higher proportion of lung remissions was observed in patients with DNA aneuploidy.     

Terminal deoxynucleotidyl transferase expression in acute myelogenous leukemia and myelodysplasia as determined by flow cytometry

The significance of terminal deoxynucleotidyl transferase (TdT) expression in acute myelogenous leukemia (AML) remains controversial. Therefore, we studied TdT expression by flow cytometry in 120 previously untreated patients with AML or myelodysplastic syndrome (MDS) to determine the distribution of TdT-positive blasts and the intensity of TdT expression and to seek clinically significant associations. TdT expression measured by flow cytometry (flow TdT%) was heterogeneous, ranging from 0.1% to 87% (median, 8.5%), and 74 patients (62%) had at least 5% TdT-positive blasts. TdT positivity was associated with the M0 or M1 subtype and with expression of CD34 and CD7. No significant correlation was found between TdT expression and type of cytogenetic abnormality or rearrangement of immunoglobulin or T-cell receptor genes. Remission lasted longer in patients with a flow TdT% < 5 than in patients with a flow TdT% > 5 (median, 95 weeks vs 55 weeks, p = 0.02); however, complete remission rates did not differ when patients were classified by initial flow TdT%. Survival was slightly better for patients with flow TdT% less than 5%. Among patients with a flow TdT% > 5%, those with a higher TdT intensity survived longer than those with a lower intensity. These data suggest that quantitative TdT measurement may contribute to prognostic estimate in AML patients.     

The significance of CD34 and TdT determinations in patients with untreated de novo acute myeloid leukemia.

The results of intensive chemotherapy given to 247 adults at the University of Maryland Cancer Center with previously untreated de novo acute myeloid leukemia (AML) were reviewed with respect to expression of terminal deoxynucleotidyl transferase (TdT) and CD34. Of the 228 patients with data for TdT, 32 (14%) had > 5% of the leukemia cells positive by an immunofluorescence assay. The median age of the TdT-positive patients was approximately 10 years less than the TdT-negative patients (50 versus 60 years). Patients with TdT-positive AML had similar median survival (12 versus 10.5 months) and complete remission (CR) rates (53 versus 59%), but a greater frequency of long-term complete responders (60 of complete remitters versus 20%, p = 0.08) than TdT-negative patients. Of 126 patients tested, 59% were CD34-negative (< 20% reactivity with leukemia cells). These 74 patients (median age 60 years) had a greater CR rate (71 versus 48%, p = 0.008) than the 52 CD34-positive patients (median age 60 years), and improved survival (p = 0.013 by Wilcoxon) although there was no difference in the duration of CR between the CD34-positive and negative groups. Of CD34-positive patients 12/52 remain in continuous CR, and 16/74 CD34-negative patients remain in continuous CR. None of eight patients strongly positive for CD34 (> 70% reactivity) remain disease-free. Positivity for TdT or CD34 was associated with less differentiated AML. Of CD34-positive patients, 44% had FAB M0/M1 morphology versus 13% of CD34-negative patients (p = 0.0001); similarly, 47% of TdT-positive patients were FAB M0/ML1 versus 25% of TdT-negative patients (p = 0.01). Of seven patients with FAB M4E0, five were CD34-positive. Of the 12 CD34-positive survivors, four had FAB M4E0. Thus CD34 expression predicts for CR rate and overall survival in adults with AML. TdT expression does not significantly affect overall outcome but may be associated with longer CR durations.     

Chk1表达与急性髓系白血病细胞多药耐药的关系及临床意义

目的通过检测急性髓系白血病（acute myeloid leukemia,AML）患者的骨髓中单个核细胞上细胞周期检测点激酶1（checkpoint kinase 1,Chk1）的表达,探讨Chk1表达水平与急性髓系白血病临床疗效及预后的关系。方法分析48例急性髓系白血病患者,按临床疗效将其分为完全缓解组和难治耐药组,应用RT-PCR和Western-blot分别检测Chk1 mRNA、蛋白质及磷酸化水平的表达,比较两组间及各组治疗前后Chk1表达水平的差异及其与AML缓解率、复发、无瘤生存期和总生存期的关系。结果 Chk1mRNA及蛋白表达水平在完全缓解组和难治耐药组组间及治疗前后差异无统计学意义（P〉0.05）;Chk1磷酸化（P-Chk1）水平在难治耐药组治疗前后分别为1.17±1.32、2.27±0.98,完全缓解组为0.81±0.62、1.07±0.96,治疗前两组间P-Chk1水平的表达差异无统计学意义（P〉0.05）,治疗后,难治耐药组明显高于完全缓解组,差异有统计学意义（P〈0.05）,且难治耐药组治疗后P-Chk1水平明显高于治疗前,差异有统计学意义（P〈0.05）,完全缓解组治疗前后差异无统计学意义（P〉0.05）;本研究以治疗后P-Chk1/β-actin的比值≥1.0定为P-Chk1阳性表达,根据此标准,难治耐药组P-Chk1阳性表达率为70.6%,显著高于完全缓解组19.4%（P〈0.05）。P-Chk1阳性患者的完全缓解率为37.5%,与P-Chk1阴性患者（78.12%）相比,差异有统计学意义（P〈0.05）;P-Chk1阳性患者复发率高、无瘤生存期和总生存期均短于阴性患者,差异有统计学意义（P〈0.05）。结论 DNA损伤后P-Chk1水平的升高影响了AML细胞对药物的敏感性,P-Chk1阳性表达与AML低解率、高复发率、短的无瘤生存期及总体生存期密切相关,提示Chk1的活化状态参与调控白血病细胞耐药的形成,故推测P-Chk1水平可作为判断急性髓系白血病临床疗效及预后的指标之一。     

Terminal deoxynucleotidyl transferase in acute myeloid leukaemia

Between January 1980 and May 1981, 1966 marrow or blood samples from leukaemia patients were tested for terminal deoxynucleotidyl transferase (TdT) using nuclear immunofluorescence. The cells were also tested with a panel of immunological markers including monoclonal antibodies. Of 869 TdT positive cases detected, 555 were diagnosed as ALL and 32 as blast crisis of CGL; 226 were provisionally diagnosed as ‘acute leukaemia’ and finally diagnosed as ALL partly on the basis of immunological data; 56 TdT⁺ cases were provisionally diagnosed as acute non-lymphocytic or myeloid leukaemia; 266 cases of AML and 177 cases of CGL in blast crisis were TdT negative.Eleven of the above ‘AML’ cases were anti-cALL⁺ as well as TdT⁺ and were re-diagnosed and treated successfully as cALL. The remaining 45 were anti-cALL negative and finally diagnosed and treated, at least initially, as AML. Eleven of these cases had only 5–10% TdT⁺ cells which could have been normal, non-myeloid cells. Twenty cases had 11–50% TdT⁺ cells and 14 cases had 50–100% TdT⁺ cells. Of these latter two groups, details on 28 patients were available for evaluation. Three cases on review had no definitive myeloid cytochemistry and were haematologically AUL with a null-ALL phenotype (TdT⁺ DR⁺ cALL^?). In 14 cases there was a large overlap (>75%) of the proportion of cells with myeloid cytochemistry (Sudan black, peroxidase or esterases) and TdT; individual blast cells were therefore expressing these markers concurrently. In the remaining cases, mixtures of TdT negative myeloid and TdT⁺ (lymphoid?) cells may have co-existed although this was not proven unequivocally. Twenty-two cases of newly diagnose TdT⁺ ‘AML’ received induction chemotherapy for AML (DAT regime) and only six (37%) obtained a complete remission.It is concluded that TdT positive ‘myeloid’ leukaemias do occur, albeit infrequently (approx. 5%) and may have a relatively poor prognosis.     

Hepatocyte growth factor levels in bone marrow plasma of patients with leukaemia and its gene expression in leukaemic blast cells.

Hepatocyte growth factor (HGF) has been known as a multiple function factor, which also stimulates early haematopoiesis. In this study, we found that HGF was expressed at both the RNA and protein levels in acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML). In patients with AML (n = 20) and CML (n = 5), bone marrow plasma HGF concentrations were 20.44 +/- 6.26 (mean +/- s.e.) ng ml-1 and 7.17 +/- 0.53 ng ml-1 respectively. These were significantly higher (P < 0.01) than the value for normal subjects (n = 26): mean 0.92 +/- 0.09 ng ml-1. Constitutive HGF production was observed in freshly prepared leukaemic blast cells from three patients with high HGF levels of bone marrow plasma. Expression of HGF mRNA was correlated with bone marrow plasma HGF levels. After complete remission was obtained in six patients, bone marrow plasma HGF levels were significantly decreased. In contrast, the HGF mRNA was less abundantly expressed in acute lymphoid leukaemia (ALL). In patients with ALL (n = 5), bone marrow plasma HGF concentration (0.69 +/- 0.14 ng ml-1) remained low within the value for normal subjects. These results suggest that some populations of myeloid lineage cells have the ability to produce HGF.     

Cytogenetic association and prognostic significance of bone marrow blast cell terminal transferase in patients with acute myeloblastic leukemia

One hundred ninety-two patients with previously untreated AML had TdT studies performed on their presenting BM aspirate specimens. Thirty-seven patients (19%) had greater than 5% TdT-positive (TdT+) blasts in their BM, as determined by an indirect immunofluorescence technique. CR rates were similar in both groups of patients (20/37 vs. 97/155, p = not significant) as were remission durations and median survivals. In the subset of patients younger than 60 years, patients with TdT+ blasts had an increased median survival (110 vs. 54 weeks, p = 0.1) compared with those having TdT- blasts. Six of 37 patients with TdT+ findings had t(8;21) translocations compared to 5 of 155 with TdT- findings (16% vs. 3%, p less than 0.01). Patients with more than 50% BM blast cells showing TdT positivity at diagnosis tended to be younger than those with TdT- (mean age 30.5 years and 50.3 years, p = 0.04). The presence of TdT+ blast cells in the initial marrow in patients with AML may be associated with specific cytogenetic abnormalities and may identify subsets of patients who have improved prognoses.