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PubMed2004

FLJ10849, a septin family gene, fuses MLL in a novel leukemia cell line CNLBC1 derived from chronic neutrophilic leukemia in transformation with t(4;11)(q21;q23).

A t(4;11)(q21;q23) has been described in 50-70% of cases of infant acute lymphoblastic leukemia and, less frequently, in cases of pediatric and adult acute lymphoblastic leukemia and acute myeloid leukemia (AML). In t(4;11)(q21;q23) leukemias, the AF4 gene has been cloned as a fusion partner of the MLL gene. A human myeloid leukemia cell line, chronic neutrophilic leukemia (CNL)BC1, was established from a peripheral blood specimen of a patient with CNL in leukemic transformation. As with the original leukemia cells, the established line had a t(4;11)(q21;q23). We showed that the MLL gene on 11q23 was fused to the FLJ10849 gene on 4q21. The protein encoded by FLJ10849 belongs to the septin family, sharing highest homology with human SEPT6, which is one of the fusion partners of MLL in t(X;11)(q13;q23) AML. Our results suggest that FLJ10849 might define a new septin family particularly involved in the pathogenesis of 11q23-associated leukemia. The established cell line, CNLBC1, could provide a useful model for analyzing the pathogenesis of MLL-septin leukemias and chronic neutrophilic leukemia.

Amino Acid Sequence↗
PubMed1983

Autologous and allogeneic typing of human leukemia cells: definition of surface antigens restricted to lymphocytic leukemia cells.

Serum from a patient (CO) with acute lymphoblastic leukemia was reactive in immunoadherence assays with autologous leukemia cells but not with autologous blood lymphocytes or bone marrow cells during complete remission. Extensive absorption tests with an array of leukemia cells and normal cells were performed in order to define the specificity of the reaction. The autologous leukemia reactivity was either completely or partially absorbed with acute lymphoblastic leukemia cells obtained from 10 of 14 patients but not with acute nonlymphoblastic leukemia cells or normal hematopoietic cells. Some cultured lymphocytic leukemia lines also showed expression of the antigen. The absence of alloantibodies in CO's serum detectable in our assay allowed direct testing of CO's serum on allogeneic target cells. The results of these tests correlated with the results of absorption tests, indicating that small populations of antigen-positive cells were not missed with absorption tests. In addition, absorption tests with CO-positive allogeneic leukemia target cells showed the same pattern of antigen distribution as tests with autologous targets. CO reactivity was not removed by absorption with cell lines expressing human T-cell leukemia virus, nor did CO's serum react with adult T-cell leukemia cells from three patients.

Antigens, Neoplasm↗
PubMed2006

Pioglitazone inhibits the growth of human leukemia cell lines and primary leukemia cells while sparing normal hematopoietic stem cells.

Peroxisome proliferator-activated receptors (PPARs) compose a subfamily of nuclear hormone receptors functioning as transcriptional regulators. Originally, the PPARgamma ligand known as thiazolidinedione (TZD) was used for the treatment of diabetic patients. However, recent studies have shown that TZD also has an antitumor effect that inhibits cell growth in several types of human malignant neoplasms, including leukemia cell lines. Since pioglitazone is the only TZD currently available in clinics in Japan and the role of TZD in normal human hematopoietic cells or primary leukemia cells has not been previously reported, we investigated the effect of pioglitazone on human normal hematopoietic progenitor cells, primary leukemia cells, and leukemia cell lines (HL60, K562, U937, HEL, CEM, Jurkat, and NALM1). Pioglitazone inhibited the proliferation of leukemia cells in a dose-dependent manner. The viable cell numbers of HL60, K562, and Jurkat leukemia cell lines were profoundly reduced when the cells were cocultured with pioglitazone. Colony formation in the leukemia cell lines as well as the primary leukemia cells was significantly inhibited to 20-71% and 1-25% of that in control cultures by the addition of 100 and 300 microM of pioglitazone, respectively. However, the CFU-E and CFU-GM colonies of cells obtained from healthy volunteers were not altered in the presence of 100 microM of pioglitazone. Pioglitazone (300 microM) induced slight decrease of CFU-E and CFU-GM. BFU-E was more sensitive to pioglitazone than CFU-E and CFU-GM. Pioglitazone-induced growth inhibition in HL60 cells was associated with cell cycle arrest at the G1 phase, as has been reported for another TZD, troglitazone. Similar levels of PPARgamma protein were observed in both leukemia and normal bone marrow cells by Western blotting, suggesting that the expression of PPARgamma protein was not associated with the inhibitory potency of pioglitazone. In conclusion, our results suggest that pioglitazone may offer a new therapeutic approach to aid in the treatment of leukemia.

Cell Line, Tumor↗
PubMed1989

Cell surface antigens of radiation leukemia virus-induced BALB/c leukemias defined by syngeneic cytotoxic T lymphocytes.

Two cell surface antigens of mouse leukemias were defined by BALB/c cytotoxic T lymphocytes (CTL) generated against syngeneic radiation leukemia virus (RadLV)-induced leukemia, BALBRV1 or BALBRVD. Hyperimmunization of BALB/c mice with irradiated leukemias followed by in vitro sensitization of primed spleen cells resulted in the generation of CTL with high killing activity. The specificity of CTL was examined by direct cytotoxicity assays and competitive inhibition assays. A shared cell surface antigen, designated as BALBRV1 antigen, was detected by BALB/c anti-BALBRV1 CTL. BALBRV1 antigen was expressed not only on RadLV-induced BALB/c leukemias except for BALBRVD, but also on spontaneous or X-ray-induced BALB/c leukemias, chemically-induced leukemias with the H-2d haplotype and some chemically-induced BALB/c sarcomas. In contrast, a unique cell surface antigen, designated as BALBRVD antigen, was detected by BALB/c anti-BALBRVD CTL. BALBRVD antigen was expressed only on BALBRVD, but not on thirty-nine normal lymphoid or tumor cells. These two antigens could be distinguished from those previously defined on Friend, Moloney, Rauscher or Gross murine leukemia virus (MuLV) leukemias, or MuLV-related antigens. Both cytotoxic responses were blocked by antisera against H-2Kd, but not H-2Dd. The relationship of BALBRV1 antigen and BALBRVD antigen to endogenous MuLV is discussed with regard to the antigenic distribution on tumor cell lines.

Animals↗
PubMed1980

Myeloblastic and lymphoblastic markers in acute undifferentiated leukemia and chronic myelogenous leukemia in blast crisis.

Blast cells were obtained from 17 patients with acute undifferentiated leukemia and 13 patients with chronic myelogenous leukemia in blast crisis. The blasts were tested with anti-i serum in cytotoxicity tests and with antisera to myeloblastic leukemia-associated antigens in immunofluorescence tests. The terminal deoxynucleotidyl transferase (TDT) content of the blasts was also measured. Lymphoblasts react strongly with anti-i, do not react with anti-myeloblast serum, and have high levels of TDT; myeloblasts react weakly with anti-i, do not react with anti-myeloblast serum, and have very low levels of TDT. Of the 17 patients with acute undifferentiated leukemia, there were six with blasts which reacted like lymphoblasts, six with blasts which reacted like myeloblasts, and five with blasts bearing different combinations of these lymphoblastic and myeloblastic markers. Eight of the 11 patients with lymphoblastic or mixed lymphoblastic-myeloblastic markers, but only one of the six with myeloblastic markers, achieved complete or partial remission in response to therapy. Thus, in acute undifferentiated leukemia, classification of blasts with these markers may be of prognostic value. Of the 13 patients with chronic myelogenous leukemia in blast crises, the markers were concordant (for myeloblasts) in only two cases. Three of the 13 patients had TDT-positive blasts, but the reactions of these cells with anti-i and with anti-myeloblast serum differed from those seen with lymphoblasts from patients with acute lymphoblastic leukemia. Although the cell involved in "lymphoid" blast crisis of chronic myelogenous leukemia is similar in many respects to that involved in acute lymphoblastic leukemia, these cells are not identical.

Adult↗
PubMed1994

Induction of graft-versus-leukemia (GVL) activity in murine leukemia models after IL-2 pretreatment of syngeneic and allogeneic bone marrow grafts.

To investigate GVL effects, Balb/c mice (H-2d) received 5 x 10(5) A20 (B cell leukemia) or 1 x 10(6) WEHI-3 (myelomonocytic leukemia) cells. These cell lines lead to death after a median of 19 (WEHI-3) or 30 days (A20). A lethal dose of total body irradiation followed by syngeneic BMT resulted in significantly prolonged survival of leukemia-bearing animals. Transplantation of (C57 x Balb/c)F1 (H-2bxd) allogeneic, but GVH-non-reactive marrow grafts differentially influenced the relapse rates in the two leukemia models. Whereas allogeneic BMT reduced the relapse rates in A20-bearing mice, the leukemia-free survival was not improved in mice bearing the leukemia WEHI-3 compared with syngeneic BMT. Pre-treatment of allogeneic (C57 x Balb/c)F1 or syngeneic Balb/c marrow cells with 200 U/ml IL-2 for 24 h did not reduce relapse rates in animals inoculated with A20 leukemia cells compared with unmanipulated bone marrow. In contrast, IL-2 treatment of syngeneic or allogeneic GVH non-reactive donor marrow significantly decreased the relapse rate in mice inoculated with WEHI-3 leukemia cells. The NK cell-mediated lysis of cultured leukemia cells was determined in vitro using a conventional 56Cr-release assay. Our data revealed a strong correlation between the level of natural killer activity determined in vitro and GVL activity in vivo.

Animals↗
PubMed2004

Clinical relevance of survivin as a biomarker in neoplasms, especially in adult T-cell leukemias and acute leukemias.

Survivin has been identified as one of the top 4 transcripts among 3.5 million human transcriptomes uniformly up-regulated in cancer tissues but not in normal tissues. Therefore, we quantitatively determined the messenger RNA (mRNA) expression profile for survivin by a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) technique in 113 patients with leukemias, such as adult T-cell leukemia (ATL), acute lymphoid leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia in crisis, and chronic lymphocytic leukemia (CLL), and in 25 cell lines, including 7 ATL cell lines and 15 solid-tumor cell lines. Furthermore, we examined whether the plasma level of survivin protein as measured by enzyme-linked immunosorbent assay (ELISA) substituted for mRNA expression by PCR quantification. Gene expression was quantitatively confirmed to be up-regulated in approximately 90% of ATL and acute leukemia cases and in all of the cell lines tested, whereas it was down-regulated in almost all cases of CLL. Furthermore, with respect to the interpretation of the gene expression findings, attention was paid to standardization with a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in the real-time PCR quantification, because the variability in GAPDH expression among the different cell types was significant. GAPDH expression was relatively low in ATL cells and high in ALL and AML cells. The rates of increase in the levels of survivin protein in the plasma of ATL patients and in the supernatants from in vitro cultures of solid-tumor cell lines were low compared with rates of increase of the mRNA and protein level in the cells, suggesting that the protein levels in plasma do not always reflect survivin expression in tumor cells. Our findings indicate the potential clinical relevance of survivin quantified by real-time PCR but not for the protein level in plasma as determined by ELISA, especially in cases of ATL and acute leukemias.

Acute Disease↗
PubMed2005

Investigation of the bovine leukemia virus proviral DNA in human leukemias and lung cancers in Korea.

The bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis. This study investigated the presence of the BLV in leukemia (179 acute lymphoblastic leukemia, 292 acute myeloid leukemia and 46 chronic myelogenous leukemia cases) and 162 lung cancer patients (139 adenocarcinoma, 23 squamous cell carcinoma) to determine if the BLV is a causative organism of leukemia and lung cancer in Koreans. A BLV infection was confirmed in human cells by PCR using a BLV-8 primer combination. All 517 cases of human leukemia and 162 lung cancer were negative for a PCR of the BLV proviral DNA. In conclusion, although meat has been imported from BLV endemic areas, the BLV infection does not appear to be the cause of human leukemia or lung cancer in Koreans. These results can be used as a control for further studies on the BLV in Koreans.

Acute Disease↗
PubMed2000

Identification and molecular characterization of CALM/AF10fusion products in T cell acute lymphoblastic leukemia and acute myeloid leukemia.

The t(10;11)(p12-p13;q14-q21) observed in a subset of patients with either acute lymphoblastic leukemia or acute myeloid leukemia has been shown to result in the fusion of AF10 on chromosome 10 with CALM (also named CLTH) on chromosome 11. AF10 was originally identified as a fusion partner of MLL in the t(10;11)(p12-p13;q23) observed in myeloid leukemia. CALM is a newly isolated gene, cloned as the fusion partner of AF10 in the monocytoid cell line, U937. In order to understand the relationship between MLL, AF10, CALM and the leukemic process, fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction were used to study a series of nine leukemia patients with a t(10;11). Six had myeloid leukemia (AML-M0, AML-M1, AML-M4 and AML-M5) and three had T cell lymphoblastic leukemia. We identified four different CALM/AF10 fusion products in five patients and AF10/CALM reciprocal message in one. We conclude that fusion of CALM and AF10 is a recurring abnormality in both lymphoid and myeloid leukemias of various types including AML-M5, and that the breakpoints in the two types of leukemia do not differ. Our data indicate that the CALM/AF10 fusion product on the der(10) chromosome is critical to leukemogenesis. Leukemia (2000) 14, 100-104.

Acute Disease↗
PubMed1991

Chronic lymphocytic leukemia and hairy-cell leukemia.

The chronic lymphoid leukemias are a heterogeneous group of disorders with different immunologic, biologic, and clinical features. The most common of these are the B-cell diseases, chronic lymphocytic leukemia and its variants, including prolymphocytic leukemia and hairy cell leukemia. The increased use of immunophenotyping has identified a number of other less common but related disorders. Despite being clonal disorders, the chronic B-cell leukemias exhibit immunologic abnormalities in multiple other lineages, the mechanism for which is not clear. Fludarabine, 2'-deoxycoformycin, and 2-chlorodeoxyadenosine are purine analogues that have advanced the treatment of chronic B-cell leukemias. Fludarabine appears to be the single most effective agent for chronic lymphocytic leukemia, while 2'-deoxycoformycin and 2-chlorodeoxyadenosine are both extremely effective in hairy cell leukemia. A recently completed comparison of alpha-interferon with 2'-deoxycoformycin in hairy cell leukemia may redefine the standard therapy for this disorder. Continued interaction between laboratory and clinical scientists is essential for continued progress in these diseases.

Adult↗
PubMed1981

Selective host range restriction of goat cells for recombinant murine leukemia virus and feline leukemia virus type A.

We isolated a strain of normal goat fibroblasts which was uniquely selective in that it allowed the replication of xenotropic murine leukemia virus but not polytropic recombinant murine leukemia virus. In addition, feline leukemia virus type A replication was severely diminished in these goat cells, whereas feline leukemia virus type B and feline endogenous RD114-CCC viruses replicated efficiently. No other known cells exhibit this pattern of virus growth restriction. These goat cells allow the study of xenotropic murine leukemia virus in mixtures which also contain recombinant murine leukemia virus and may be helpful in eliminating feline leukemia virus type which often coexists in feline sarcoma or leukemia virus mixtures with other feline leukemia virus types.

Animals↗
PubMed1991

Acute myeloid leukemia induction by amphotropic murine retrovirus (4070A): clonal integrations involve c-myb in some but not all leukemias.

Amphotropic murine retrovirus 4070A was demonstrated to be highly leukemogenic when inoculated intravenously into adult DBA/2 mice that were undergoing an intense chronic inflammatory response, but was nonleukemogenic in the absence of inflammation. The virus-induced promoonocytic leukemias, designated AMPH-ML, are similar morphologically and in cell surface marker expression to monocytic leukemias, called MML and MF-ML, previously shown to be induced by Moloney murine leukemia virus and MF-3 virus (a recombinant between Friend murine leukemia virus and Moloney murine leukemia virus) and resemble certain mature acute monocytic leukemias in humans (AML subtype M5). Approximately two-thirds of the AMPH-MLs (subgroup I) were demonstrated to have alterations in the 5' end of the c-myb locus, an event which occurs in 100% of MML and MF-ML. Data indicate that proviral insertions in AMPH-ML subgroup I resulted in aberrant c-myb mRNA expression and truncation of its translation product at the amino terminus. Approximately one-third of the AMPH-MLs (subgroup II) had not undergone any DNA rearrangements at the c-myb locus. In addition, their transcripts and protein products were of normal size. These latter leukemias also had not undergone DNA rearrangements in c-myc, although retroviruses expressing myc have previously been shown to induce monocyte-macrophage tumors in mice undergoing a chronic inflammation. That subgroup II leukemias had at least one clonal viral insertion suggests that there may be other sites in the cellular genome that can be activated by insertional mutagenesis in these murine acute monocytic leukemias.

Animals↗
PubMed2003

Risk and prognosis of central nervous system leukemia in patients with Philadelphia chromosome-positive acute leukemias treated with imatinib mesylate.

PURPOSE: In patients with acute leukemias, a lymphoid phenotype, the presence of a Philadelphia chromosome (Ph), and inadequate central nervous system (CNS)-directed prophylactic therapy are risk factors for CNS involvement. Imatinib mesylate has promising single-agent antileukemic activity in patients with advanced Ph(+) acute leukemias. It was the aim of this analysis to determine the incidence of, and risk factors associated with, meningeal leukemia during imatinib monotherapy. STUDY DESIGN: We analyzed 107 consecutive patients with relapsed or refractory Ph(+) acute lymphoid leukemia (ALL; n = 65) or chronic myeloid leukemia blast crisis (n = 42) who were enrolled in successive Phase II trials of single-agent imatinib and who did not receive routine prophylactic intrathecal chemotherapy. RESULTS: CNS leukemia developed in 13 of 107 patients (12%) and was associated primarily with a lymphoid or bilineage phenotype (12 of 78; 15%) and with imatinib refractory Ph(+) ALL (5 of 19; 26%). Meningeal leukemia did not occur among patients who received prior prophylactic cranial irradiation. The median survival with combined CNS and systemic disease was 108 days (range, 58-141), with no patient surviving long term. In contrast, two of three patients with exclusively meningeal leukemia achieved prolonged molecular remissions with intrathecal chemotherapy, cranial irradiation, and continued imatinib. CONCLUSIONS: Patients with Ph(+) ALL are at considerable risk of meningeal leukemia during imatinib monotherapy and should routinely receive CNS prophylaxis. Although the prognosis with combined meningeal and systemic relapse is dismal, patients with an isolated meningeal relapse may still achieve sustained remissions. The optimal type of CNS-directed treatment and the extent of protection afforded by prophylactic cranial irradiation remain to be defined.

Adolescent↗
PubMed1995

Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL).

Criteria for the immunological classification of acute leukemias are proposed by a recently established European group designated EGIL. The main aims of EGIL are to establish guidelines for the characterization of acute leukemias based on marker expression and provide a uniform basis for the diagnosis of the various types of these hemopoietic malignancies which should be helpful for future multinational clinical and laboratory investigations. Within the two major types (B and T cell lineage) of acute lymphoblastic leukemia (ALL), several groups are delineated according to the degree of cell differentiation. Within the acute myeloid leukemias (AML), only three subtypes as defined by the FAB classification: M0-AML, M6-AML and M7-AML, can be unequivocally defined by immunological markers; prospective studies are undertaken to see whether characteristic immunological profiles are associated with particular AML subtypes defined by specific cytogenetic abnormalities. Criteria for the definition of biphenotypic acute leukemia (BAL) are devised and a scoring system is outlined aimed to distinguish BAL from those acute leukemias with expression of a marker from another lineage. In addition, an uncommon subset of acute leukemias with no evidence of lymphoid or myeloid differentiation is recognized and the useful panel of markers to investigate and establish the cell nature of the acute leukemias is outlined. EGIL will focus in the future on testing the reproducibility of the proposed guidelines, particularly those for BAL, assessing their clinical value within a framework of multicentric trials and setting up uniform methodological criteria.

Acute Disease↗
PubMed1977

In vitro induction of cell-mediated immunity to murine leukemia cells. II. cytotoxic activity in vitro and tumor-neutralizing capacity in vivo of anti-leukemia cytotoxic lymphocytes generated in macrocultures.

The main findings of the present study are: (a) highly reactive cytotoxic lymphocytes (CTL) against syngeneic and allogeneic murine leukemia cells were generated in vitro in macro 'one-way' mixed leukocyte-tumor cultures (MLTC). Cultures set up in large tissue culture flasks contained up to 400 X 10(6) normal spleen cells (responder cells) and 20--40 X (10(6) mitomycin C-treated leukemia cells (stimulator cells). Successful sensitization in macrocultures was greatly dependent upon the responder cell density and the responder/stimulator cell ratio. Cytotoxic activity, as measured by the 51Cr-release assay, peaked on day 5--7. (b) Sensitized 'memory' lymphocytes produced in primary MLTC could be restimulated with the original tumor cells to give a more rapid and stronger secondary cytotoxic response. (c) lymphocytes sensitized to allogeneic leukemia cells reacted equally well with sensitizing leukemia cells and with the corresponding normal lymphoid target cells, whereas lymphocytes sensitized to syngeneic leukemia cells did not react with the homologous normal lymphocytes. (d) Cryopreserved normal splenocytes and leukemia cells were as efficient as fresh cells in generating allogeneic and syngeneic CTL. (e) Using a Winn-type tumor neutralization assay, it was shown that both allogeneic and syngeneic splenocytes sensitized in vitro to EL4 leukemia (of C57BL/6 mice) and to YAC leukemia (of A mice) were capable of preventing tumor growth in the syngeneic host, whereas cultured normal splenocytes frequently showed a tumor-enhancing effect. Long-term survivors, remaining after inoculation of leukemia cells and sensitized lymphocytes, also became resistant to a tumor challenge that was up to 10,000 greater than the minimum lethal dose.

Animals↗
PubMed1998

Possible induction of graft-versus-leukemia effect against a leukemia refractory to antileukemia response in ordinary MHC-compatible, allogeneic bone marrow transplantation.

We previously indicated that intensity of the graft-versus-leukemia (GVL) effect varied among different leukemias in MHC-compatible, allogeneic bone marrow transplantation (BMT). Cellular factors responsible for differences in intensity of the GVL effect were examined by using two types of leukemias, i.e., a resistant leukemia (LE750) and a sensitive leukemia (8313) to induction of the GVL effect in MHC-compatible, allogeneic BMT of leukemia-bearing host. Resistance of LE750 leukemic cells to induction of the GVL effect could not be attributed to either less sensitivity to lysis by minor H antigen-specific, cytotoxic T cells or to an immunosuppressive activity of LE750 leukemic cells in leukemia-bearing host, when compared with the case of the sensitive leukemia (8313). To investigate the significance of the dose effect of effector cells for induction of the GVL effect, we used CD8+ T cells of AKR donor mice, which were shown to preferentially induce the GVL effect with hardly any lethal graft-versus host disease against C3H recipient mice, enabling us to increase the number of CD8+ T cells used in the allogeneic donor inoculum. The results suggested that the outcome of the antileukemic response in allogeneic BMT of leukemic recipients may be determined, at least in part, by the balance between the size of leukemic cells surviving and repopulating in the recipients after BMT and the number of antileukemic effector cells. The results furthermore indicated that when donors with T-cell subsets that preferentially induce an antileukemic response with reduced graft-versus-host disease are available, a more effective antileukemic response is inducible even against advanced leukemias.

Animals↗
PubMed1995

Long-term follow-up of adults with acute lymphoblastic leukemia in first remission treated with chemotherapy or bone marrow transplantation. The Acute Lymphoblastic Leukemia Working Committee.

OBJECTIVE: To determine whether the conclusions of a 1991 study, which showed that adults with acute lymphoblastic leukemia in first remission had similar leukemia-free survival rates when treated with chemotherapy or HLA-identical sibling bone marrow transplantation, remain valid after more than 4 years of additional follow-up. DESIGN: Retrospective comparison of two cohorts of patients using left-truncated Cox regression to adjust for differences in baseline characteristics and time to treatment. SETTING AND PATIENTS: Chemotherapy recipients were 484 consecutive patients with acute lymphoblastic leukemia in first remission treated in 44 hospitals in Germany that were participating in two consecutive trials of the German Acute Lymphoblastic Leukemia Therapy Trials Group. Transplant recipients were 234 consecutive recipients of HLA-identical sibling bone marrow transplants for acute lymphoblastic leukemia in first remission in 98 centers, worldwide, reporting data to the International Bone Marrow Transplant Registry. INTERVENTIONS: Intensive combination chemotherapy or HLA-identical sibling bone marrow transplantation preceded by high-dose chemotherapy with or without total body irradiation. MEASUREMENTS: Relapse, treatment-related mortality, and leukemia-free survival rate 9 years after first complete remission. RESULTS: The conclusions of our previous analyses were confirmed. Actuarial relapse probabilities at 9 years were 66% (95% CI, 61% to 70%) for chemotherapy and 30% (CI, 22% to 37%) for transplantation (P < 0.0001). The leukemia-free survival rates at 9 years were 32% (CI, 27% to 37%) for chemotherapy and 34% (CI, 28% to 40%) for transplantation (P > 0.02). CONCLUSIONS: Fewer relapses but more treatment-related deaths were seen with transplantation than with chemotherapy. Thus, leukemia-free survival rates were similar in adults receiving transplantation and adults receiving chemotherapy for acute lymphoblastic leukemia in first remission.

Antineoplastic Agents↗
PubMed2003

Induction of T-cell immunity against leukemia by dendritic cells pulsed with total RNA isolated from leukemia cells.

OBJECTIVES: To assess the feasibility and efficacy of eliciting leukemia-specific T-cell responses in syngeneic mice in vitro and in vivo using dendritic cells (DCs) pulsed with total RNA from leukemia cells. METHODS: DCs generated from bone marrow culture in vitro in the presence of combined cytokines were pulsed with cellular total RNA isolated from cultured L615 cells by cationic lipid 1,2-dioleoyloxy-3-(trimethylammonium) propane (DOTAP). T-cell responses were evaluated by in vitro proliferation, and cytotoxicity assay. And in vivo immune protection and prognosis of mice with leukemia were studied. RESULTS: DCs pulsed with total RNA isolated from cultured L615 cells (DCs/RNA) were remarkably effective in stimulating L615-specific T-cell response in vitro, but did not cross-react with other leukemia cells from syngeneic mice. Vaccination of naive mice with viable DCs/RNA vaccine was able to partly protect from challenge with a lethal dose of live L615 cells, leading to low leukemia incidence and overall survival prolongation. Statistically significant survival was also observed in a low lethal dose of L615-bearing mice that received treatment using viable DCs/RNA vaccine alone, suggesting that systemic administration of IL-2 could enhance the anti-tumor efficacy of leukemia RNA/DCs vaccine. CONCLUSIONS: These data support the use of DCs/RNA vaccine as a feasible and effective route to elicit leukemia immunity against unidentified leukemia-associated antigens for treatment of leukemia-bearing animals.

Animals↗