Monoclonal antiglycophorin as a probe for erythroleukemias

A monoclonal antibody (LICR.LON.R10) specific for the major sialoglycoprotein of the erythroid cell membrane, glycophorin A (alpha), has been used to test the possibility that "cryptic" erythroleukemia may be diagnosed as acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML). In addition to 27 overt erythroleukemias, 724 leukemias, including 329 ALL (103 in relapse), 205 AML, and 109 blast crises of Ph1-positive chronic myeloid leukemia, were analyzed. Twenty cases with a significant proportion of glycophorin-A-positive (gA+) cells were found; 8 of these (5 AML and 3 blast crises of chronic myeloid leukemia, CML) had an obvious erythroid component, but 12 others were diagnosed as AML (2), AMML (1), CML in myeloid blast crisis (4) or megakaryoblastic blast crisis (1), acute megakaryoblastic leukemia (2), or acute lymphoblastic leukemia (2). The latter two patients had no immunologic evidence supporting a diagnosis of ALL and were resistant to chemotherapy. We conclude that AML and ALL only very rarely express gA, and these are probably genuine "cryptic" erythroleukemias. Other gA+ leukemias (megakaryoblastic and CML blast crises) may arise from bi- or pluripotent stem cells and contain distinct and separable blast cell populations.     

肺耐药蛋白在急性白血病中的表达及意义

目的 探讨急性白血病（AL）患者骨髓单个核细胞肺耐药蛋白（LRP）的表达及意义。方法 采用LRP单克隆抗体、流式细胞技术分别测定15例单纯缺铁性贫血患者（对照组）和65例AL患者（AL组）LRP的表达率。结果 LRP的表达率在初治和复发／难治急性淋巴细胞白血病（ALL）患者分别高于初治和复发／难治急性髓细胞白血病（AML）患者（P均〈0．05）；AML中M5亚型表达率高于M3亚型（P〈0．05）。初治及复发／难治LRP（＋）者缓解率明显低于LRP（-）者（P〈0．05）。结论 LRP的表达与AL患者临床预后密切相关，化疗前检测LRP表达率有助于个体化治疗和预测疗效。     

Expression of Fas receptor and soluble Fas ligand (sFasL) concentration in acute leukemia

Apoptosis mediated by the interaction of cytotoxic T lymphocyte with blast cell via Fas receptor/Fas ligand (FasL) pathway is a one of the mechanisms of immunological leukemia surveillance. There is few data on possible blocking of Fas receptor by soluble form of Fas (sFasL) present in serum and the role of blast cells as the source of this ligand. Forty-eight patients with de novo diagnosis of acute leukemia, 32 with myeloblastic (AML) and 16 with acute lymphoblastic leukemia (ALL) were studied. Fas expression on bone marrow leukemic blasts was determined by flow cytomertic immunofluorescent analysis and serum concentration of sFasL assessed at presentation, in remission and in relapse. Blasts of all patients expressed Fas at variable degree (0.8 to 100%). Fas expression was significantly higher on myelo--than on lymphoblasts. There was no relation between degree of Fas expression at diagnosis and remission rate. Concentration of sFasL in acute leukemia patients at diagnosis was significantly higher than in healthy control group, decreased to normal values in remission and rose again in relapse. There was a negative correlation between Fas expression on blasts and sFasL concentration at the time of diagnosis. Results obtained suggest that blast cells could be the source of soluble FasL in acute leukemia patients and that sFasL serum concentration could be used for monitoring of disease activity.     

Expression of p16INK4a,p15INK4b,p21WAF1/Clip1 cell cycle inhibitors on blastic cells in patients with acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL)

Cyclin-dependent kinases (cdk) play the important role in neoplastic transformation. Their activity depends on interaction with proteins called inhibitors. There are two groups of inhibitors: INK4 (p16INK4a, p15INK4b, p18INK4c, p19INK4d) and proteins p21WAF1/Clip1, p27Kip1, p57Kip2. Alteration of inhibitors expression was assessed in acute lymphoblastic leukemia (ALL) and in acute myeloblastic leukemia (AML), but the results are not clear. The aim of our study was to estimate p16INK4a, p15INK-4b, p21WAF1/Clip1 expression in blast cells in patients with AML and ALL by cytochemistry method and to compare with the result of treatment. Forty-two patients were included in the study, 23 with AML and 19 with ALL. Expression of inhibitors was considered as positive when detected in > 5% of blast cells. Complete remission (CR) rate in patients with positive expression p16INK4a and p15INK4b was statistically significantly higher than in patients with negative expression: for p16INK4a chi 2 = 7.78, p < 0.01, for p15INK4b, chi 2 with Yates' modification = 3.94, p < 0.05. There was no difference in CR rate in patients with positive and negative p21WAF1/Clip1 expression. Moreover the patients with simultaneous expression of three inhibitors reached CR more often than the others: chi 2 = 7.43, p = 0.01 for AML and chi 2 = 6.74, p < 0.01 for ALL. Our study indicates that estimation of p16INK4a, p15INK4b, p21WAF1/Clip1 expression in blast cells can be used as prognostic factor in acute leukemia.     

The effects of high dose methylprednisolone on apoptosis in children with acute lymphoblastic leukemia

Rapid leukemic cell kill at initial diagnosis of patients with acute lymphoblastic leukemia (ALL) has been shown to be associated with a favorable outcome. The aim of the present study was to investigate the effect of high dose methylprednisolone (HDMP) on in vivo blast cell apoptosis in children with ALL. Annexin V-binding and Fas (CD95), Fas ligand (FasL; CD95L), and Bcl-2 expression in PB blasts were determined in newly diagnosed children with ALL before and 4, 24, 96 h after initiation of HDMP treatment (n=20) or conventional dose steroids (CDS) (n=10) as the control group. A decrease in absolute blast count (from 40.8 x 09 to 21.4 x 109/l) associated with an increase in apoptosis (14.2 to 26.9%) (P < 0.05) was detected 4 h after initiation of HDMP. A significant increase in Fas and FasL expression was detected 96 h after HDMP. There was no significant change in apoptosis, Fas and FasL expression from baseline in the control group treated with CDS. The changes in Bcl-2 expression after treatment was not significant in both groups. The results of this preliminary study have shown that HDMP treatment was effective in inducing immediate (within 4 h) blast cell apoptosis. The contribution of Fas/FasL interaction in the rapid component of cell kill remains to be determined, as the increase in the expression of these molecules was evident later.     

Clinical significance of P-glycoprotein expression and function for response to induction chemotherapy, relapse rate and overall survival in acute leukemia

BACKGROUND AND OBJECTIVES: A multidrug-resistance (MDR) phenotype mediated by P-glycoprotein (P-gp) contributes to chemotherapy failure in acute leukemia. However, the exact prognostic significance of this resistance mechanism is still unclear, mostly due to methodologic problems in P-gp detection. We therefore investigated, whether P-gp expression levels or functional P-gp activity better predict response to induction chemotherapy, relapse rate and overall survival in acute leukemia. DESIGN AND METHODS: We examined cell samples of 121 adults with de novo acute myeloid leukemia (AML) and 102 children with newly diagnosed acute lymphoblastic leukemia (ALL) for P-gp expression and functional P-gp activity by flow cytometry. P-gp function was determined by the rhodamine 123 (rh123)-efflux test (AML n=121, ALL n=102) and P-gp expression levels using the P-gp specific monoclonal antibodies (moabs) MRK-16 (AML n=51, ALL n=31), 4.E3 (AML n=35, ALL n=32), or UIC-2 (AML n=68, ALL n=50). We correlated our findings with the immunophenotype, FAB morphology, cytogenetics and clinical data of the examined patients. RESULTS: P-gp expression levels as detected by MRK-16 and 4.E3 were very low and did not differ between AML and ALL as estimated using relative fluorescence intensity (RFI) values and D-values by Kolmogorow-Smirnov (KS) statistics. For moab UIC-2, P-gp expression levels were higher in AML than in ALL. Within AML, moab UIC-2 mainly reacted with myelomonocytic-differentiated leukemic cells of the FAB M4/5 subtypes. No correlation between P-gp expression levels as detected by MRK-16, 4.E3 or UIC-2 and the response to induction chemotherapy or relapse rate, both in AML and ALL, was observed. However, a prognostic impact of P-gp expression levels on overall survival in AML was seen for moab MRK-16. Moreover, within AML, P-gp function was higher in immature blast cells as defined by immunophenotype and FAB morphology and correlated with response to induction chemotherapy, relapse rate, overall survival as well as cytogenetic risk groups. In ALL, the overall functional P-gp activity was lower than in AML and did not correlate with immunophenotypical subgroups, response to induction chemotherapy, relapse rate or overall survival. INTERPRETATION AND CONCLUSIONS: Our data demonstrate a prognostic impact of P-gp in AML but not ALL and indicate that the functional rh123-efflux assay should be preferred for flow-cytometric P-gp evaluation in acute leukemia compared with P-gp expression analysis by monoclonal antibodies.     

Constitutive expression levels of CD95 and Bcl-2 as well as CD95 function and spontaneous apoptosis in vitro do not predict the response to induction chemotherapy and relapse rate in childhood acute lymphoblastic leukaemia

CD95 (Fas/APO-1) expression and function and Bcl-2 expression, as well as spontaneous apoptosis in vitro, have been shown to be predictive markers for the in vivo response to chemotherapy in acute myeloid leukaemia (AML). To determine the clinical significance of apoptosis-regulating factors in acute lymphoblastic leukaemia (ALL), we investigated cell samples of children with ALL who had been included in the German ALL Berlin-Frankfurt-Münster (BFM) study using flow cytometry for constitutive expression levels of CD95 (n = 110) and Bcl-2 (n = 110). Furthermore, we determined the extent of spontaneous apoptosis in vitro (n = 102) and susceptibility to anti-CD95-induced apoptosis (CD95-sensitivity) (n = 97). We correlated these findings with the functional activity of the multidrug resistance (MDR)-associated P-glycoprotein (P-gp), as detected by the rhodamine123 efflux test, immunophenotype, cytogenetics and clinical data of the patients examined. Good responders to initial prednisone therapy ('prednisone response') revealed significantly higher Bcl-2 expression levels [5.4 +/- 3.4 relative fluorescence intensity (RFI), n = 68] than poor responders (3.7 +/- 2.6 RFI, n = 42; P = 0.002). There was no significant correlation between the other investigated parameters and prednisone response. Moreover, neither the CD95 and Bcl-2 expression levels nor the extent of spontaneous apoptosis in vitro, CD95 sensitivity or P-gp function were correlated with the response to induction chemotherapy or relapse rate, either for B-cell precursor ALL or T-cell ALL. No consistent pattern of change in CD95 (n = 10) and Bcl-2 expression (n = 9) was noted in cases studied at both initial diagnosis and relapse. In conclusion, our findings underline the different cell biological features of primary AML and ALL cells.     

Differential excretion of modified nucleosides in adult acute leukemia

Excretion of modified nucleosides in urine was measured in 23 adults with acute leukemia to determine correlation of nucleoside excretion with disease activity. In addition, differences in excretion between patients with acute lymphoblastic leukemia (ALL) and patients with acute myeloid leukemia (AML) were established. Six modified nucleosides were resolved and quantitated by reversed-phase high-performance liquid chromatography (HPLC). Patients with ALL at initial diagnosis or in relapse had significantly higher concentrations of 1-methylinosine and N2,N2-dimethylguanosine in their urine compared to patients in remission (p less than 0.01, p less than 0.05, respectively). One patient with ALL was followed with serial nucleoside determinations over a period of 18 mo; nucleoside excretion correlated closely with disease activity. Nucleoside excretion in patients with AML did not change significantly with disease activity. Considering only those patients at initial diagnosis or in relapse, excretion of 1- methylinosine and N2,N2-dimethylguanosine was significantly higher in ALL than in AML (p less than 0.01, p less than 0.05, respectively). Thus, urinary excretion of 1-methylinosine and N2,N2-dimethylguanosine by adults with acute leukemia may prove to be valuable clinically in following disease activity in patients with ALL and in distinguishing patients with ALL from those with AML.     

Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisense oligonucleotide,in combination with chemotherapy in refractory or relapsed acute leukemia

Overexpression of Bcl-2 is a potential mechanism for chemoresistance in acute leukemia and has been associated with unfavorable clinical outcome. We hypothesized that down-regulation of Bcl-2 would restore chemosensitivity in leukemic cells. To test this hypothesis, we performed a phase 1 study of G3139 (Genasense, Genta, Berkeley Heights, NJ), an 18-mer phosphorothioate Bcl-2 antisense, with fludarabine (FL), cytarabine (ARA-C), and granulocyte colony-stimulating factor (G-CSF) (FLAG) salvage chemotherapy in patients with refractory or relapsed acute leukemia. Twenty patients with refractory or relapsed acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) were enrolled. G3139 was delivered by continuous infusion on days 1 to 10. FLAG chemotherapy was administered on days 5 to 10. Common side effects of this combination included fever, nausea, emesis, electrolyte imbalance, and fluid retention that were not dose limiting. Plasma pharmacokinetics of G3139 demonstrated steady-state concentration (Css) within 24 hours. Of the 20 patients, 9 (45%) had disease response, 6 (5 AML, 1 ALL) with complete remission (CR) and 3 (2 AML and 1 ALL) with no evidence of disease but failure to recover normal neutrophil and/or platelet counts or to remain in remission for at least 30 days (incomplete remission). Bcl-2 mRNA levels were down-regulated in 9 of the 12 (75%) evaluable patients. This study demonstrates that G3139 can be administered safely with FLAG chemotherapy and down-regulate its target, Bcl-2. The encouraging clinical and laboratory results justify the current plans for a phase 3 study in previously untreated high-risk AML (ie, age at least 60 years).     

急性白血病细胞体外对Jurkat细胞凋亡的影响

为探讨白血病细胞凋亡相关基因 (Fas)的功能性表达情况 ,将 2 7例白血病患者的白血病细胞与 Jurkat细胞体外孵育后 ,用原位末端标记法 (TUNEL )测定单纯 Jurkat细胞 (对照组 )、不加和加入不同浓度抗凋亡相关基因配体 (Fas L)的 Jurkat细胞凋亡率。结果显示 ,不加抗 Fas L 急性非淋巴细胞白血病组 (ANL L 组 )与对照组比较 ,凋亡率明显增高 (P<0 .0 1) ,急性淋巴细胞白血病组 (AL L 组 )与对照组比较仅轻度增高 (P<0 .0 5 ) ,两者均随细胞浓度的增加而凋亡率增高 ;ANL L组加与不加抗 Fas L 相比凋亡率明显减少 (P<0 .0 1) ,随抗 Fas L浓度的增加而凋亡率减少 ,AL L 组加与不加抗 Fas L 相比凋亡率轻度减少 (P<0 .0 5 ) ,也随抗 Fas L 浓度的增高而减少 ,但不如 ANL L组凋亡率变化明显。提示急性白血病细胞存在 Fas L的功能性表达 ,ANL L较 AL L的 Fas L表达高     

C-kit receptor tyrosine kinase (CD117) expression and its positive predictive value for the diagnosis of Thai adult acute myeloid leukemia

We examined the expression of c-kit receptor tyrosine kinase in 195 Thai adult patients with acute leukemia and determined its specificity and predictive values for the diagnosis of adult acute myeloid leukemia (AML). CD117 was used to detect c-kit expression on CD45 and side-scatter-gated blast cells by flow cytometry. Of 163 AML cases, 67% expressed CD117. None of acute lymphoid leukemia (ALL) had CD117 expression, except one case of T-ALL. The majority of AML patients carrying t(8;21), inv(16), and t(15;17) had high CD117 expression. High proportion of AML cases without c-kit expressed monocytic markers. Significant associations between CD117 and CD34 (P<0.001), CD13 (P=0.006), CD7 (P=0.034), and CD19 (P<0.001) were found in AML cases. The calculated specificity of CD117 for the diagnosis of AML was 0.97, which was higher than CD13 (0.78) and CD33 (0.75) but comparable to MPO (0.97). The positive predictive value (PPV) of CD117 for AML was 0.99, with the negative predictive value of 0.35. In conclusion, the majority of Thai adult AML cases expressed c-kit. C-kit is infrequently expressed in ALL and appeared to be specific for AML with high PPV. Future targeting therapy using c-kit as a therapeutic target should benefit the majority of Thai AML patients who had high c-kit expression.     

Evaluation of Apaf-1 and procaspases-2, -3, -7, -8, and -9 as potential prognostic markers in acute leukemia

Recent studies have suggested that variations in levels of caspases, a family of intracellular cysteine proteases, can profoundly affect the ability of cells to undergo apoptosis. In this study, immunoblotting was used to examine levels of apoptotic protease activating factor-1 (Apaf-1) and procaspases-2, -3, -7, -8, and -9 in bone marrow samples (at least 80% leukemia) harvested before chemotherapy from adults with newly diagnosed acute myelogenous leukemia (AML, 42 patients) and acute lymphocytic leukemia (ALL, 18 patients). Levels of each of these polypeptides varied over a more than 10-fold range between specimens. In AML samples, expression of procaspase-2 correlated with levels of Apaf-1 (R(s) = 0.52, P <.02), procaspase-3 (R(s) = 0.56, P <.006) and procaspase-8 (R(s) = 0.64, P <.002). In ALL samples, expression of procaspases-7 and -9 was highly correlated (R(s) = 0.90, P <.003). Levels of these polypeptides did not correlate with prognostic factors or response to induction chemotherapy. In further studies, 16 paired samples (13 AML, 3 ALL), the first harvested before induction therapy and the second harvested at the time of leukemia regrowth, were also examined. There were no systematic alterations in levels of Apaf-1 or procaspases at relapse compared with diagnosis. These results indicate that levels of initiator caspases vary widely among different leukemia specimens but cast doubt on the hypothesis that this variation is a major determinant of drug sensitivity for acute leukemia in the clinical setting. (Blood. 2000;96:3922-3931)     

Circulating transferrin receptor in acute leukemias.

Serum transferrin receptor (s-TR) levels in acute leukemia patients were measured by a recently developed sandwich radioimmunoassay. The mean s-TR level for normal subjects (n = 205) was 246 +/- 79 (mean +/- 1 SD) ng/ml. The values for patients with untreated acute myelocytic leukemia (AML, n = 18) and untreated acute lymphocytic leukemia (ALL, n = 14) were 398 +/- 175 ng/ml and 479 +/- 176 ng/ml, respectively, both of which were significantly higher than those for the normal subjects (AML, p < 0.02; ALL, p < 0.05). When complete remission was achieved with initial remission induction therapy, s-TR decreased to 262 +/- 47 ng/ml (n = 22, 12 AML and 10 ALL), returning to normal levels. There was a good correlation between s-TR levels and the number of leukemic cells in peripheral blood (r = 0.743, n = 32, p < 0.01). In two patients with AML, serial changes of s-TR values and numbers of blast cells in the peripheral blood and bone marrow occurred in a parallel manner. If, therefore, this assay for s-TR can be made more sensitive, it may become useful for assessing acute leukemia activity and for monitoring the effects of therapy.     

The relationship between bcl-2 expression and response to chemotherapy in acute leukaemia

Summary. Immunocytochemistry was used to assess bcl-2 expression in blasts obtained from the bone marrow of 28 patients with acute lymphoblastic leukaemia (ALL) (16 children and six adults at presentation and three children and three adults on relapse) and 20 with acute myeloid leukaemia (AML) (19 adults and one child, 13 with de novo AML, 11 at presentation and two on relapse, and seven secondary to myelodysplasia or chronic myeloid leukaemia). Slides were examined both for the percentage of positive cells and for the intensity of staining using a five-point scale. There was a statistically significant increase in both the percentage of positive cells seen (P < 0.002) and the intensity of staining (P < 0.01) between samples obtained at relapse and those at presentation in ALL. There was a significantly greater intensity of staining in cells from patients with ALL (P < 0.05) and AML (P < 0.05) who failed to achieve remission after chemotherapy than in those who responded. The intensity of staining in cases of secondary AML was lower than that in de novo disease (P < 0.01). These results suggest that expression of bcl-2 may be an important prognostic feature in both de novo AML and in ALL, but not in secondary AML.     

Differential expression of the carcinoembryonic antigen-related cell adhesion molecules panCD66, CD66a,CD66c and of sialyl-Lewis x (CD15s) on blast cells of acute leukemias

Expression of CD66 has been reported to occur on blast cells from children with acute lymphoblastic leukemia (ALL), but little is known about the differential expression pattern of panCD66 and other members of the CD66 family on blast cells from patients with acute myeloid leukemia (AML). We have performed flow cytometry immunophenotyping on blast cells from 28 patients with acute myeloid leukemia (AML), 13 patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and 7 patients with T-ALL using monoclonal antibodies (mAbs) against panCD66 (clone D14HD11), CD66a (clone 4.3.17), CD66c (clone 9A6) and CD15s. Expression of the panCD66 mAb was found to be positive in 13 of 28 patients with AML (46%) and in 6 of 13 patients with BCP-ALL (46%) but negative for all the seven patients with T-ALL. In AML, panCD66, CD66a and CD66c were more frequently coexpressed with CD65, CD15 and CD64 than with CD13, CD33 or the two progenitor markers CD34 and CD117. In contrast to CD15, the expression of the sialylated Lewis X (CD15s) was associated with CD117 positivity in the majority of AML cases (64 vs. 85%, P = 0.043). Radioimmunotherapeutic strategies targeting CD66 antigens should consider the heterogeneous expression pattern of CD66 molecules in acute leukemias especially in AML where expression is correlated with mature granulomonocytic cells but not with CD34 and CD117 positive progenitor cells.     

Impact of luteinizing hormone suppression on hematopoietic recovery after intensive chemotherapy in patients with leukemia

Treatment of acute leukemia with intensive chemotherapy leads to an increased risk of myelosuppression. Luteinizing hormone (LH) blockade improves hematopoietic recovery in mice after radiation or chemotherapy, through protection of the hematopoietic stem cells which express the LH receptor. We hypothesized that LH blockade improves hematopoietic recovery following intensive chemotherapy in patients with leukemia. We conducted a retrospective analysis on pre-menopausal women with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who received intensive chemotherapy and leuprolide given for abnormal uterine bleeding prevention or treatment. Given that leuprolide is more commonly administered in younger patients, we performed propensity score matching between the leuprolide (AML n=64; ALL n=49) and control groups (AML n=128; ALL n=98 patients). Patients with AML who received leuprolide had an additional increase of 13.8x10⁹/L/year in their platelet count, and a 0.19x 10⁹/L/year increase in their lymphocyte count after chemotherapy compared to control (P=0.02; P=0.03 respectively). Those with ALL who received leuprolide had an additional increase of 0.37x10⁹/L/year in their absolute neutrophil count (P=0.02). In AML, leuprolide was associated with higher long-term hemoglobin levels (P<0.001) and less blood transfusions (mean, 23.9 vs. 34.7 units; P=0.002) compared to control. In a multivariate analysis, leuprolide was identified as an independent factor predicting improved hemoglobin levels, lymphocyte and platelet counts in AML. In conclusion, leuprolide use in leukemia patients receiving intensive chemotherapy was associated with improved long-term blood count recovery and with decreased transfusion requirements in AML.     

Detection of p53 oncogene in acute-leukemia cells by immunoperoxidase technique

Expression of p53 oncogene in blast cells may have prognostic importance in acute leukemia. Simple and reliable methods which could detect enhanced p53 expression in leukemia cells would be important for follow-up studies of leukemia patients in remission. We used immunoperoxidase (IP) technique with an anti-p53 monoclonal antibody PAb421 to study the expression of p53 in leukemia cells. The expression of p53 was studied in 9 cell lines and 17 de novo acute leukemia (9 acute myeloid leukemia [AML], 8 acute lymphoblastic leukemia [ALL]) patients. The expression of p53 was demonstrated in non-T non-B cells and Burkitt's lymphoma cell lines, but neither in two myeloid leukemia cell lines nor in normal lymphoid cells after mitogenic stimulation. p53 expression was demonstrated in 7 cases (2 AML, 5 ALL) but only in ALL cases the percentage of positive of cells was over 20%. Bone marrow cells from patients were studied also after short-term culture (AML patients); in 1 case the number of PAb421-positive cells rose significantly after culture. These data suggest that IP staining with PAb421 can be used to demonstrate high p53 expression in B cell leukemias.     

急性淋巴细胞白血病复发预测的研究

目的 :探讨急性淋巴细胞白血病 (ALL)的复发与P16蛋白缺失和bcl 2蛋白及血清可溶性白细胞介素 2受体 (sIL 2R)表达的关系。方法 :采用双抗体夹心酶联免疫吸附法 (ELISA)测定sIL 2R ,采用免疫组织化学方法测定P16蛋白、bcl 2蛋白的表达水平。结果 :在ALL中 ,P16蛋白缺失率、bcl 2蛋白阳性率及sIL 2R表达 ,复发组显著高于初诊组 (P <0 .0 1) ,初诊组显著高于完全缓解组 (CR组 ) (P <0 .0 1) ;初诊和复发ALL患者P16蛋白缺失率、bcl 2蛋白及sIL 2R表达与外周血白细胞总数 (r =0 .779,0 .886 ,0 .86 0 )、外周血幼稚细胞比值 (r =0 .82 1,0 .80 9,0 .813)和肝脾肿大呈正相关 (r =0 .84 6 ,0 .75 5 ,0 .84 0 ) (P <0 .0 1)。结论 :监测P16蛋白缺失、bcl 2蛋白及sIL 2R表达水平可预测ALL的复发。