Low incidence of TEL/AML1 fusion and TEL deletion in Korean childhood acute leukemia by extra-signal fluorescence in situ hybridization

TEL/AML1 fusion in acute leukemia results from cryptic translocation of chromosome 12 and 21, the presence of which suggests a favorable prognosis. The incidence of TEL/AML1 fusion in B-lineage ALL is approximately 25%, but the incidence in Korea has not yet been reported. To investigate the incidence of TEL/AML1 fusion and TEL deletion, bone marrow specimens from 77 Korean children with newly diagnosed acute leukemia were analyzed by FISH. We applied extra-signal FISH to discriminate a true TEL/AML1 fusion from a false-positive fusion signal. To determine the cut-off value of the TEL/AML1 fusion signal, 20 normal bone marrow specimens and 28 normal peripheral blood specimens were also analyzed. The frequency of patients with TEL/AML1 fusion was 13.3% (4 cases) among 30 B-lineage ALL and 9.5% among 42 ALL. One TEL/AML1 fusion-positive patient was also found among 4 acute biphenotypic leukemias. TEL/AML1 fusion was not found in any samples from patients with T-lineage ALL or AML. The incidence of TEL deletion was 6.7% (2 cases) among 30 B-lineage ALL and 4.8% among 42 ALL. The incidences of TEL/AML1 fusion and TEL deletion in Korean children with acute leukemia appear to be lower than those in other countries, suggesting a racial difference.     

Impact of cellular CD71 (transferrin receptor 1) expression in Egyptian acute leukemia: correlation with clinicopathologic features

Cellular transferrin receptor 1 (CD71) has been identified as a proliferation marker. Inferior outcome with higher expression was observed in many solid tumors. This study objected to assess the expression of CD71 in patients with acute leukemia and to address its prognostic significance and relations to clinicopathologic features. The study included 34 acute myeloid leukemia (AML) and 64 acute lymphoblastic leukemia (ALL) newly diagnosed cases from Mansoura Oncology Center. CD71 was analyzed on blast cells by flow cytometry. CD71 expression was significantly elevated in both AML and ALL. Antigen expression apparently increased in T-ALL, while in AML there was a trend toward a gradual increase of antigen expression in relation to maturation evidence of myeloid subtypes. CD71 expression correlated positively with total leukocyte count in ALL cases and negatively with platelet count in AML cases. In ALL, higher CD71 expression was associated with higher relapse rate and was an independent prognostic factor of overall survival (HR 1.8; 95 % CI 1.2–4.1). In conclusion, CD71 is overexpressed in acute leukemia; it predicts adverse clinical outcome in ALL. In addition, CD71 antagonism could be a possible therapeutic target in acute leukemia.     

Utility of white blood cell suspect flags and histogram pattern in the detection of acute leukemia by Advia-60 automated hematology analyzer

Blood samples from patients with acute leukemia, when analyzed with automated hematology counters, tend to introduce inaccuracies in the automated differential count and can cause diagnostic confusion without providing definite clues to the presence of abnormal cells. We designed this study to assess the utility of white blood cell (WBC) flags and histogram pattern generated by Advia-60 automated hematology analyzer in the recognition and categorization of acute leukemia. Data printouts of 31 newly diagnosed cases of acute leukemia, 22 with acute myeloid leukemia (AML) and 9 with acute lymphoblastic leukemia (ALL) were reviewed. All cases of AML and ALL generated the WBC suspect blastflag M2 associated with two of the non blast suspectflags G1 and G2. Among the cases of AML, 95.5% of the WBC histogram patterns were definitive of the presence of abnormal cells and were indicative of the myeloid nature of cells. Only 44.4% of the histograms in the cases of ALL could be definitive of the presence of abnormal cells and 33.3% were indicative of their lymphoid nature. Significantly, 55.5% of the histograms in ALL were normal. The false positives for both AML and ALL were 10.5% when only WBC flagging was considered and were reduced to 0.05% when the flags were combined with histogram patterns for interpretation. Combined flagging and histogram recognition can be of aid in identifying cases of acute leukemia and the morphologist can then assess these samples further. This ensures that cases of acute leukemia, especially in high output laboratories, are not inadvertently missed.     

Myeloperoxidase gene expression in acute leukemias

Since myeloperoxidase (MPO) is considered to be a critical marker of differentiating acute myelogenous leukemia (AML) from acute lymphocytic leukemia (ALL), the analysis of MPO gene expression may provide further insight into the leukemia classification and the lineage fidelity of leukemia cells. By Northern blot hybridization using full-length MPO cDNA as a probe, approximately 66% of AML cells (3/4 M1 cases, 2/4 M2 cases, 15/15 M3 cases, 11/15 M4 cases, and 2/12 M5 cases) were found to express MPO mRNAs, whereas none of 18 ALL cases did. MPO mRNA was detectable when AML cells contained at least 10% peroxidase-positive cells. APL (M3) cells expressed high levels of mRNA in accordance with heavy staining for peroxidase.     

Acute myeloid and lymphoblastic leukemia in adults. The course of the disease in 315 patients from one region, during a ten-year period

In a ten-year retrospective singlecenter study of a nonselected patient population, we describe our experience with an unchanged chemotherapy regimen for 264 patients with acute myeloid leukemia (AML) and 51 patients with acute lymphoblastic leukemia (ALL). In the AML group, 85 patients could not receive specific antileukemic treatment because of uncontrollable bleeding, infection or organ failure, but 179 were fit for remission-induction therapy with cytarabine and daunorubicin, resulting in complete remission in 79 patients. During treatment, 54 patients died of resistant disease or complications. The median duration of survival of the patients in complete remission was 18-24 months (n = 79) compared with 1-2 months for patients in partial or no remission (n = 100). As maintenance chemotherapy, thioguanine, cytarabine and daunorubicin were given for one year. In the ALL group 50 of 51 patients received remission-induction therapy with vincristine, prednisone and Adriablastin, resulting in complete remission in 39 of the patients. The median duration of survival of the patients in complete remission was nine months (n = 39) compared with 2-3 months for patients not in remission (n = 12). Central nervous system prophylaxis with intraspinal methotrexate and cranial irradiation was given, followed by methotrexate and Purinetol for three years as maintenance chemotherapy. The remission rate for AML and adult ALL was 44% and 78%, respectively. The major Cause of death after first complete remission was leukemic relapse in boths groups, with a median survival time after relapse of 3-4 months for 48 AML and six months for 30 ALL patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Study of tumor cells sensitivity in patients with acute leukemia to cytokines and their combined use with drugs in vitro by MTT analysis

MTT analysis has yielded data on the sensitivity of leukemia cells isolated from 64 patients with acute leukemia to the cytokines G-KSF?, GM-KSF, interferon-alpha 2b and their combined use with drugs, such as cytosar, vepeside, doxorubicin, vincrastine, L-asparaginase. The mean in vitro survival of leukemia cells in children with acute lymphoblast cell leukemia (ALCL) was 1.9 times less than that in acute myeloblast cell leukemia (AMCL) (p < 0.001), that in new cases of ALL was 2.3 times less than in relapses (p = 0.024). The stimulating effect of GM-KSF on the survival rates of leukemia cells was seen in 64.7% of patients with AML. That of GM-KSF was recorded in 21.4% of cases. The survival of lymphoblast cells isolated from children with ALL did not differ greatly in the absolute majority of cases (by more than 30%) in the presence of growth factor in the medium. The cytotoxicity of XII with medium growth factor decreased in most cases. However, some cases (more frequently in AML than ALCL) displayed a higher cytotoxicity of XII, particularly cytosar in the presence of G-KSF and GM-KSFG; LC50 of Ara-C decreased by 30% or more in the presence of growth factor in 36% of patients. Incubation with interferon alpha 2b caused a reduction in the survival of leukemia cells, which was more pronounced in children with ALL. Interferon-alpha 2b caused an increase in the cytotoxic effect of XII on leukemia cells in ALL to a greater extent; cytosar, vepeside, and doxorubicin enhanced the effect by 1.47, 1.39, and 2.35 times, respectively.     

Second Hematopoietic Stem Cell Transplantation for Post-Transplantation Relapsed Acute Leukemia in Children: A Retrospective EBMT-PDWP Study

Outcome data were collected from the European Society for Blood and Marrow Transplantation registry on 373 children from 120 centers with relapsed leukemia (214 with acute lymphoblastic leukemia [ALL] and 159 with acute myelogenous leukemia [AML]) who underwent second allogeneic hematopoietic stem cell transplantation (HSCT) between 2004 and 2013. Overall survival (OS) was 38% at 2 years and 29% at 5 years, and leukemia-free survival (LFS) was 30% at 2 years and 25% at 5 years. Median follow-up after second HSCT was 36.4 months in the ALL group and 50.2 months in the AML group. In the ALL group, OS was 43% at 2 years and 33% at 5 years, and LFS was 34% at 2 years and 31% at 5 years. In the AML group, OS was 32% at 2 years and 24% at 5 years, and LFS was 24% at 2 years and 17% at 5 years. The 2-year nonrelapse mortality (NRM) rate was 22% in the ALL group and 18% in the AML group. Favorable prognostic factors (P?<?.05) for OS and LFS included >12 months between transplantations and chronic graft-versus-host disease after the first HSCT (in both groups), complete response before the second HSCT (ALL group only), and age >12 years (AML group only). Findings were more consistent over time in the ALL group, with no significant differences between 2-year and 5-year rates of relapse, NRM, and LFS. Children with relapsed acute leukemias have a substantial likelihood of long-term survival following second HSCT. Given the many novel targeted and immunomodulation therapies currently under development, it is important to identify specific patient subpopulations that may benefit from a second HSCT compared with those better suited to new approaches.     

Haploidentical hemopoietic stem cell transplantation for the treatment of high-risk leukemias: How NK cells make the difference

T-cell-depleted hematopoietic stem cell (HSC) transplantation from an HLA-haploidentical relative (Haplo HSCT) may represent a suitable and effective transplant option, as it is capable of rescuing not only adult patients with high-risk acute myeloid leukemias (AML) but also children with relapsed acute lymphoblastic leukemia (ALL), as shown by the two representative cases presented in this study. In Haplo HSCT, the anti-leukemia effect is mediated by “alloreactive” (i.e. KIR/HLA-mismatched) NK cells originated from donor HSCs. The availability of suitable KIR-specific monoclonal antibodies allows the prompt identification of alloreactive NK cell subsets as well as their quantification. This is important for selection of the most suitable donor and evaluation of the generation and persistence of these alloreactive NK cells after transplantation. In view of the favorable clinical outcome of children with chemo-resistant ALL, Haplo HSCT from an NK-alloreactive relative could become a first option in these high-risk leukemia patients.     

用Flu和Ara-c的改良方案预处理后自体造血干细胞移植治疗急性白血病临床观察

目的评价采用氟达拉滨（Flu）和阿糖胞苷（Ara-c）改良的预处理方案进行自体造血干细胞移植（AHSCT）治疗急性白血病的安全性和疗效。方法27例急性白血病患者,其中男性18例,女性9例;年龄12～51岁,中位年龄20岁。急性淋巴细胞白血病（ALL）21例;急性髓细胞性白血病（AML）5例。均采用包含Flu和Ara-c的预处理方案进行AHSCT,方案包括全身照射（TBI）7～8Gy或白消胺（Bu）3.2mg/（kg·d）×3d联合环磷酰胺（Cy）50mg/（kg·d）×2d、Flu30mg/（m^2·d）×3d、Ara-c2g/（m^2·d）×3d。结果除1例患者早期死亡外,所有患者均成功重建造血系统,中性粒细胞恢复至大于0.5×109/L、血小板恢复至20×109/L的中位时间分别为11（9～19）d和16（10～55）d。预处理过程中无严重不良事件发生,移植相关死亡率（TRM）7.4%（2例）。4年总体复发率（RR）、TRM和无病生存率（DFS）分别为38.8%±10.3%、9.3%±5.7%、60.8%±9.8%。结论在AHSCT治疗急性白血病中,以Flu、Ara-c改良的TBI/Cy或Bu/Cy预处理方案髓外毒性小,无病生存率较高,可作为急性白血病预处理的一种有效选择。     

Influence of harringtonine on human leukemia cell differentiation

The influence of low doses of harringtonine (Ht) on differentiation of blood cells from acute myeloblastic (AML) and lymphoblastic leukemia (ALL) patients diagnosed according to FAB classification was tested. Out of five cases of ALL only in one case differentiation into mature lymphocytes appeared. In two cases out of four of AML differentiation was seen in one case into more mature granulocytic series and in another one into monocytes. Two out of 3 acute myelomonocytic leukemias (AMMOL) differentiated, one into more mature granulocyte cells and one into monocytes. One of our patients with AML (M2) in relapse was treated with ht using HOAP (harringtonine, oncovin, adriblastine, prednisone) schedule with good but transient effect. Prior to therapy in vitro tests performed with ht showed differentiation of leukemic cells into more mature granulocyte cells.     

Plasma soluble interleukin-2 receptor (sIL-2R) levels in patients with acute leukemia

The plasma soluble interleukin-2 receptor (sIL-2R) level was higher in 137 patients with acute leukemia (1,489 +/- 1,798 U/ml, including 98 cases of acute myeloid leukemia (AML), 1,063 +/- 1,414 U/ml, and 39 cases of acute lymphoblastic leukemia (ALL), 2,561 +/- 2,194 U/ml), compared to 49 normal control subjects, 421 +/- 151 U/ml). The ALL patients showed elevated plasma sIL-2R levels more frequently than the AML patients (92.3% vs 44.9%). No patient with either hypoplastic AML or AML with multilineage dysplasia and only 1 of 13 patients with acute promyelocytic leukemia (APL) had an elevated plasma sIL-2R level. All the My+ ALL patients (15 cases) showed elevated plasma sIL-2R levels. Plasma sIL-2R levels were significantly lower after chemotherapy in the ALL patients, but were not significantly lower in the AML patients. IL-2R was expressed on the leukemic cells in 36 (53.7%) of 67 AML and in 9 (21.4%) of 42 ALL cases. None of the AML M3, M4, M5, M6, or M7 subgroups showed IL-2R expression. The My+ ALL patients (42.9%, 6/14) showed IL-2R expression more frequently than the other ALL subgroups (10.7%, 3/28) (p = 0.025). The plasma sIL-2R level was correlated with the proportion of leukemic cells expressing IL-2R in acute leukemia. However, there were many cases, particularly ALL cases, who had elevated plasma sIL-2R levels without IL-2R expression on their leukemic cells. These results suggest that the plasma sIL-2R level is a valuable marker for monitoring ALL after chemotherapy, particularly in My+ ALL cases, and that the T cell immune reaction to leukemia appears to be much higher in ALL patients than in AML patients.     

Anti-CD10 immunoperoxidase staining of paraffin-embedded acute leukemias: comparison with flow cytometric immunophenotyping

CD10 is common in B-precursor acute lymphoblastic leukemia (ALL) but is rare in acute myeloid leukemia (AML). However, until recently, analysis for CD10 has generally required fresh or frozen tissue. 56C6 is a monoclonal antibody that is now commercially available for the detection of CD10 in routinely processed paraffin-embedded tissue. Immunoperoxidase stains for CD10 on paraffin-embedded bone marrow core biopsy specimens (B5-fixed, decalcified) and marrow aspirate clots (formalin-fixed) were compared with flow cytometric immunophenotyping for CD10 on fresh cell suspensions in 20 cases of AML and in 30 cases of ALL. CD10 detection by immunohistochemistry agreed with CD10 by flow cytometry in 98% (49 of 50) of acute leukemias. The results matched in 100% (20 of 20) of AML. Five percent (1 of 20) of AMLs expressed CD10. Two of the AMLs with monocytoid differentiation were interpreted as negative for CD10 by flow cytometry, although these had nonspecific dim immunofluorescence for multiple markers, including CD10, and these cases were negative by immunohistochemistry. CD10 detection by immunohistochemistry agreed with CD10 by flow cytometry in 97% (29 of 30) of ALL. Eighty-four percent (21 of 25) of B-precursor ALL and 40% (2/5) of T-lineage ALL expressed CD10 by immunohistochemistry. In 1 case of B-precursor ALL, CD10 was dimly positive in 24% of the blasts by flow cytometry but negative by immunohistochemistry. We conclude that immunohistochemical staining of paraffin-embedded tissue, either B5- or formalin-fixed, is an effective method for the detection of CD10 in acute leukemia. This technique is useful in distinguishing AML from ALL.     

基于粒子群优化算法的白血病基因表达样本分类研究

目的基于分子生物学的微阵列基因表达数据和智能优化算法对白血病肿瘤样本进行分类研究。方法给出基于粒子群优化(PSO)算法用于分类模型的训练和测试,选取含7129个基因的72个白血病基因表达样本,从中选取包含50、100和200个特征基因的3组数据,在不同基因数条件下分别执行10次分类测试。建立基于K-均值算法的分类模型,在同等条件下验证PSO算法分类性能。使用准确率、精确率、召回率、F1值等机器学习指标及Boxplot和Heatmap图谱用于分析对比。结果PSO算法用于分类测试的数据分别含20例急性淋巴细胞白血病(ALL)和14例急性髓细胞白血病(AML)样本。10次分类结果的平均分类准确率均在90%左右;PSO算法的分类准确率并不稳定,10次分类测试中,准确率的平均值和最优值间存在明显差异;ALL亚型的召回率明显高于AML亚型,均接近100%,但AML亚型的精确率明显高于ALL亚型,均接近100%,F1值可比性不大。K-均值算法与PSO算法类似,分类性能随着基因数的增加而降低;K-均值算法在200基因数条件下分类结果较差,分类稳定性和准确率均出现大幅下降,且低于同等条件下PSO算法分类结果;100个基因数条件下,ALL亚型召回率为100%,高于AML亚型;AML亚型精确率为100%,高于ALL亚型;200个基因数条件下,平均值中ALL亚型召回率和F1值高于AML亚型,AML亚型精确率高于ALL亚型,其最优值的统计学指标差异不大。相同白血病肿瘤样本的不同特征基因数条件下,PSO算法可获得较高准确率的分类结果,但分类稳定性不足,整体上优于K-均值算法。结论PSO算法能够应用于白血病基因表达样本的分类研究。     

Minimalna choroba resztkowa w ostrych białaczkach u dzieci i dorosłych

Biological and genetic heterogeneity of acute leukemias is a major cause of therapeutic difficulties. Response to chemotherapy is one of the most important prognostic factors in this group of diseases. In acute lymphoblastic leukemia (ALL), and progressively more in acute myeloid leukemia (AML), the best parameter of that response is the presence of minimal residual disease (MRD). MRD monitoring is performed based on the flow cytometer analysis of leukemic immunophenotypes or detection of gene rearrangement by PCR. Both methods are characterized by high sensitivity and specificity, which clearly distinguishes them from the standard morphologic examination. This review presents the current state of knowledge of the importance and use of MRD in children and adults, in ALL and AML, emphasizing similarities and differences. Current opinions show that the MRD is the most important prognostic factor in ALL and an important factor in AML. Based on current data in children and adults, it seems that in acute lymphoblastic leukemia, presence of MRD is a continuous variable; the older the patient, the higher the risk of MRD and therapy failure. This paper presents also a new insight to the concept of MRD, because of the presence of leukemic stem cells that survive chemotherapy in AML and any of the maturational stages of leukemia-propagating cells in ALL. This idea combines the phenomenon of drug resistance of tumor stem cells and the presence of residual cells undetectable by methods of optical microscopy after applied chemotherapy. The concept of leukemic stem cells explains the occurrence of resistant clones both in ALL and AML. Based on studies of genetic profiles, there is growing evidence to suggest that acute leukemia is a highly heterogeneous disease, which goes hand in hand with the hierarchy of leukemic stem cells and leukemia initiating cells. In the light of the current knowledge based on MRD, it seems necessary to review the concept of complete remission in MRD-positive leukemic patients.     

Use of the Technicon H-1 in the characterization of leukemias

The Technicon H-1 is a hematology analyzer that performs a complete blood cell count and white blood cell differential using both cytochemistry and flow technology. Two white blood cell cytograms are produced based on peroxidase activity and nuclear characteristics of the cells. Ninety cases of leukemia were studied. The 25 cases of acute lymphocytic leukemia (ALL) could be distinguished from the 39 cases of acute nonlymphocytic leukemia as the lymphocyte percentage was greater than 50% in the ALL cases and the mean peroxidase index value was 0 in 80% of the cases. The ALL cases and the chronic lymphocytic leukemia cases also had different cytogram patterns. Subtypes of acute nonlymphocytic leukemia could not be absolutely distinguished, although promyelocytic leukemias (M3) had characteristic cytograms and a monocyte percentage above 15% suggested a monocytic component (M4 or M5). Chronic myelogenous leukemia likewise seemed to have a recognizable pattern. Since a sample takes only 60 s to process, information is readily available. The unique data available from this instrument should provide a significant advancement in the automated hematology field.     

Differences in CD33 intensity between various myeloid neoplasms

We measured the concentration of CD33 antigen on the surface of cells in 315 bone marrow (BM) samples and 114 corresponding peripheral blood (PB) samples from patients with various leukemias (acute myeloid leukemia [AML], chronic myelogenous leukemia [CML], myeloproliferative disorder [MPD] other than CML, myelodysplastic syndrome [MDS]) and from control subjects. Overall CD33 intensity in total CD33+ cells was significantly higher in BM than in PB. CD33 intensity in total BM CD33+ cells differed significantly with the type of disease. The median number of CD33 molecules per cell was highest in AML, followed by MDS, CML, and control subjects and lowest in MPD. When only CD34+/CD33+ cells were examined, CD33 molecules per cell were highest in CD34+ cells in AML and lowest in MPD (P = .027). Patients with AML or MDS younger than 60 years had significantly higher intensity of CD33 expression on CD34+ cells than patients 60 years or older. Levels of CD33 intensity did not correlate with cytogenetics in patients with AML or MDS. There was no correlation between CD33 intensity and response to therapy or overall survival in 35 patients treated with protocols including Mylotarg. These data demonstrate variation in CD33 intensity between various leukemias.     

Pattern of leukemias: a ten-year incidence study of 242 cases

This paper presents an analysis of data collected from 242 cases of acute and chronic leukemia observed during a 10-year period. The incidence of childhood leukemia was 26.45%. In the present series, it was 35.95% for ALL, 21.9% AML, 38.4% CML and 2.89% CLL. The incidences of ALL and CML were found comparable to other series from Bombay. The geographical variations in the pattern of leukemias as observed in India are discussed.     

Syndecan-1/CD138 expression in normal myeloid,acute lymphoblastic and myeloblastic leukemia cells

Stabilization of cell surface antigens and preservation of ultrastructural integrity are important aspects of immunoelectron microscopical studies. In the present study, 4 anti-syndecan-1/CD138 (B-B2, B-B4, MI15, 1D4) monoclonal antibodies (mAbs) were applied in combination with periodatelysine-paraformaldehyde (PLP) fixation and indirect pre-embedding peroxidase electron microscopical immunocytochemistry to analyse the localization and function of these molecules in normal myeloid cells, acute lymphoblastic leukemia (ALL) cells and acute myeloblastic leukemia (AML) cells. One case of normal human bone marrow, 3 cases of untreated AML and 2 cases of untreated ALL were studied. Samples were immediately fixed for 4 h in freshly-prepared PLP fixative in 0.037 mol/L phosphate buffer, pH 7.4, containing 10 mmol/L sodium metaperiodate, 75 mmol/L lysine, and 2% paraformaldehyde. Expression of syndecan-1 was found at the plasma membrane of all cell types. Staining intensity at the membrane of AML cells was stronger than that on the membrane of normal myeloid and ALL cells. We conclude that anti-syndecan-1/CD138 mAbs in combination with the method described here are a suitable tool for detection of cell surface syndecan molecules in cells originating from progenitor cells that can differentiate in both myeloid and lymphoid cells.     

Cytokine-driven differentiation of blasts from patients with acute myelogenous and lymphoblastic leukemia into dendritic cells

We investigated the ability of both acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) blasts to differentiate into dendritic cells (DC) in vitro. Cytokine-supplemented suspension cultures of leukemic blasts in 98 patients with AML and five patients with ALL (normal karyotype, n = 2; BCR/ABL, n = 3) were performed. Mononuclear cells out of peripheral blood or bone marrow containing between 60% and 90% leukemic blasts were cultured for eight days using different growth factor combinations. The highest yield of CD1a(+)/CD14(-) cells could be obtained with stem cell factor, transforming growth factor-beta, tumor necrosis factor-alpha, GM-CSF, and FLT-3-ligand. In the AML samples the median content of CD1a(+)/CD14(-) cells after eight days of culture was 3.5% (r = 0%-82%). In five informed patients CD1a(+)/CD14(-) cells were sorted by fluorescence-activated cell sorting or immunomagnetic separation. Cytogenetic and polymerase chain reaction analyses showed known primary chromosomal aberrations (monosomy 7 and inversion 16) in the sorted fractions, respectively. Dendritic cells (DC) could be generated out of leukemic blasts in 68% of AML patients. Leukemic DC showed no phagocytosis of latex beads, but stimulated allogeneic naive cord blood-derived T cells more efficiently than did uncultured blasts. In ALL patients the median percentage of CD1a(+)/CD14(-) cells was 1.2% (r = 0.7%-3.8%) after culture. The sorted CD1(+)/CD14(-) fractions were BCR/ABL-negative when analyzed with fluorescence in situ hybridization, indicating their nonleukemic origin. Leukemic DC can be generated out of leukemic progenitors in patients with AML. These cells might become relevant for autologous and allogeneic immunotherapy in selected patients. BCR/ABL-positive lymphoblasts could not be transformed into cells with an early dendritic phenotype with the cytokines used in our experiments.