Bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(I.V.) as a novel antileukemic agent with matrix metalloproteinase inhibitory activity.

We have examined the in vitro anticancer activity of METVAN [bis(4,7-dimethyl-1,10 phenanthroline) sulfatooxovanadium(IV); VO(SO(4))(Me(2)-Phen)(2)] against acute lymphoblastic leukemia (ALL; NALM-6 and MOLT-3), acute myeloid leukemia (AML; HL-60), Hodgkin's disease (HS445), and multiple myeloma (ARH-77, U266BL, and HS-SULTAN) cell lines as well as primary leukemic cells from patients with ALL, AML, and chronic acute myeloid leukemia (CML). METVAN induced apoptosis in NALM-6, MOLT-3, and HL-60 cells in a concentration-dependent fashion with EC(50) values of 0.19 +/- 0.03 microM, 0.19 +/- 0.01 microM, and 1.1 +/- 0.2 microM, respectively. METVAN induced apoptosis at low micromolar concentrations in primary leukemic cells from patients with ALL, AML, and CML. METVAN inhibited the constitutive expression of matrix metalloproteinase (MMP)-9 protein and its gelatinolytic activity in HL-60 cells and MMP-2 as well as MMP-9 gelatinolytic activities in leukemic cells from ALL, AML, and CML patients. Furthermore, METVAN inhibited the leukemic cell adhesion to the extracellular matrix proteins laminin, type IV collagen, vitronectin, and fibronectin and the invasion through Matrigel matrix. Further preclinical development of METVAN may provide the basis for the development of more effective chemotherapy programs.     

Differentiation induction in myeloid leukemic cells

Work based on immortalised leukemic cell lines indicates that the maturation arrest in leukemia can be reversible. Successful differentiation induction would mean restoring the link between proliferation and differentiation. Human cell lines such as the promyelocytic HL-60 and the monoblastic U-937 can be induced to mature by incubation with a wide variety of agents, e.g. phorbol diesters, retinoic acid and 1,25-dihydroxycholecalciferol. In addition, mitogen-stimulated lymphocytes and some T-lymphocyte lines produce a polypeptide called the differentiation-inducing factor (DIF), which mediates maturation of HL-60 into macrophage-like cells with resulting proliferation inhibition. DIF also displays a primary growth inhibitory effect on certain subclones of the cell lines as well as on fresh clonogenic cells from patients with acute myeloid leukemia and on normal granulocyte-macrophage progenitors. Our data indicate that there is more than one way to induce differentiation in leukemia but final common pathways may exist. Complementary, synergistic, maturation effects are seen between some agents, which may become of clinical utility.     

Study of differentiation of fresh myelogenous leukemic cells by compounds that induce a human promyelocytic leukemic line (HL-60) to differentiate

The human promyelocytic leukemia cell line known as HL-60 can be triggered to mature to functional granulocytes and/or macrophages after exposure to a variety of compounds. The findings have generated enthusiasm for possible therapy of leukemia using compounds that induce leukemic cell differentiation. We investigated whether five compounds known to trigger HL-60 differentiation to granulocytes could trigger the maturation of blast cells from 12 patients with myelogenous leukemia. Maturation was judged by morphology, superoxide production, phagocytosis, expression of Fc receptors, and development of alpha-napthyl acetate esterase activity. The blast cells from most patients showed little morphological, histological or functional maturation after exposure to the various compounds as compared to the blast cells cultured without the compounds. Actinomycin was able to induce significant maturation of leukemic cells of some patients when maturation was analyzed by several statistical methods. Our study suggests that many compounds which trigger differentiation of promyelocytic leukemia cells may not trigger differentiation of less mature myeloid leukemic cells.     

Modifications in phospholipase D activity and isoform expression occur upon maturation and differentiation in vivo and in vitro in human myeloid cells.

Activation of phospholipase D (PLD) occurs in response to various stimuli and results from the activity of two isozymes, hPLD1 and hPLD2. PLD activity appears to be involved in several myeloid cell processes during their development and activation, including proliferation of myeloblasts in the bone marrow and secretion, phagocytosis and NADPH oxidase activation, essential functions of differentiated neutrophils. The present work studies PLD characteristics, activity and both isozyme expression during maturation and differentiation of myeloid cells by using three different systems: leukemic myeloblasts at different stages of maturation, terminally differentiated neutrophils ex vivo and four human myeloid cell lines, NB4, HL-60, PLB 985 and U937, induced to differentiate with alltrans retinoic acid (ATRA), a cyclic adenosine monophosphate (cAMP) analogue or both agents together. HL-60, a bipotential cell line has also been differentiated along the granulocytic pathway with DMSO and the monocytic pathway with 1,25-dihydroxy vitamin D3. In all these systems, PLD activity increases with maturation and differentiation whatever the inducer used and the granulocytic or monocytic pathways. Increase in basal activity which reflects the expression during development of both hPLD1 and hPLD2 appears to be mainly related to the former isozyme expression. Association of PLD characteristic changes with maturation and differentiation was also confirmed using two NB4 clones resistant to these processes. Comparison between PLD characteristics in myeloblasts during maturation and differentiation ex vivo and in vitro in the different cell lines demonstrated that NB4 induced to differentiate with ATRA represents the best model for further studies on the specific roles of each PLD isoform in various functions of differentiated myeloid cells.     

Cotylenin A--a plant growth regulator as a differentiation-inducing agent against myeloid leukemia

Acute myeloid leukemia (AML) is characterized by the arrest of differentiation leading to the accumulation of immature cells. This maturation arrest can be reversed by certain agents. Although differentiation therapy for patients with acute promyelocytic leukemia (APL) using all-trans retinoic acid (ATRA) has been established, the clinical response of AML patients other than those with APL to ATRA is limited. We must consider novel therapeutic drugs against other forms of AML for the development of a differentiation therapy for leukemia. Regulators that play an important role in the differentiation and development of plants or invertebrates may also affect the differentiation of human leukemia cells through a common signal transduction system, and might be clinically useful for treating AML. Cotylenin A, a plant growth regulator, is a potent and novel inducer of the monocytic differentiation of human myeloid leukemia cell lines and leukemia cells freshly isolated from AML patients.     

Arsenic trioxide and methylprednisolone use different signal transduction pathways in leukemic differentiation

Certain cell lines like HL 60 and K 562 are utilised as leukemic cell models for leukemogenesis research, which differentiate along the granulocytic and/or monocytic pathway when treated with certain inducer molecules. High dose methylprednisolone treatment has been shown to induce in vivo and in vitro differentiation of myeloid leukemia cells to mature granulocytes in patients with acute promyelocytic leukemia (APL) and other subtypes of acute myeloid leukemia (AML). Arsenic trioxide (As(2)O(3)) has been confirmed to have remission induction effects on APL. However, there are conflicting results on the effects with other AML subtypes. Also, it has been well established that the reversible phosphorylation of proteins is a major regulatory mechanism in the signal transduction pathways that control cell growth and differentiation. Serine/threonine protein phosphatases (PP) are major components of phosphorylation. In this study, we investigated the effect of As(2)O(3) on HL 60 and K 562 myeloid leukemic differentiation and compared the signalling cascades of the two inducers with respect to serine/threonine PP 1 and 2A. We utilised PP1 and PP2A inhibitors okadaic acid and calyculin A. In contrast to methylprednisolone, there was no effect of phosphatase inhibitors on As(2)O(3)-induced leukemic differentiation. Incomplete leukemic differentiation occurred with lower As(2)O(3) concentration as 10(-6)M. Unlike As(2)O(3), methylprednisolone induced complete granulocytic and/or monocytic differentiation of HL 60 and K 562 cells via upregulation of PP2A regulatory subunits. Therefore, As(2)O(3) and methylprednisolone are promising agents that have the potential to be used together in myeloid leukemic differentiation therapy.     

Reversal of human myeloid leukemia cells into normal granulocytes and macrophages: activity and intracellular distribution of catalase

The activity and intracellular distribution of catalase was studied in culture human myeloid leukemia cells before and after induction of differentiation with tunicamycin. Activity of catalase was increased 5-fold in acute myeloid leukemia cells (AML) and 3-fold in chronic myeloid leukemia cells in comparison with normal granulocytes. Tunicamycin induced differentiation of HL-60 line and primary AML line characterized by increase in phagocytic cells and changes to resemble mature myeloid cells. Fc receptors were also induced in cells after tunicamycin treatment. Induction of differentiation with tunicamycin decreased high activity of catalase in cultured leukemic cells. The results of digitonin titration experiments showed that in control granulocytes and differentiated leukemic cells most of the catalase activity is present in subcellular particles distinct from mitochondria or lysosomes. In contrast, the catalase activity in undifferentiated cells is present in the same compartment as the other cytosolic markers.     

C/EBPalpha and C/EBPvarepsilon induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene

CCAAT/enhancer binding proteins (C/EBPs) have an important function in granulocytic differentiation, and are also involved in the leukemogenesis of acute myeloid leukemia (AML). Their involvement in myelomonocytic leukemia, however, is still unclear. Therefore, the expression and function of C/EBPs in myelomonocytic cells with MLL-fusion genes were investigated. Retinoic acid (RA) induced monocytic differentiation in the myelomonocytic cell lines with MLL-fusion genes, THP-1, MOLM-14 and HF-6 cells, accompanied by monocytic differentiation with the upregulation of C/EBPalpha and C/EBPepsilon. Monocytic differentiation by RA treatment was confirmed in primary AML cells using a clonogenic assay. When the activity of C/EBPalpha or C/EBPepsilon was introduced into HF-6 cells, their cellular growth was arrested through differentiation into monocytes with the concomitant marked downregulation of Myc. Cebpe mRNA was upregulated by the induction of C/EBPalpha-ER, but not vice versa, thus suggesting that C/EBPepsilon may have an important function in the differentiation process. Introduction of Myc isoforms into HF-6 cells partially antagonized the C/EBPs effects. These findings suggest that the ectopic expression of C/EBPepsilon, as well as C/EBPalpha, can induce the monocytic differentiation of myelomonocytic leukemic cells with MLL-fusion gene through the downregulation of Myc, thus providing insight into the development of novel therapeutic approaches.     

Decrease in asparagine synthetase activity during cell differentiation of mouse and human leukemia cell lines

The activity of asparagine synthetase decreased almost 50% during dexamethasone-induced mouse myeloid leukemia M1 cell differentiation. This enzyme activity also declined significantly during differentiation of the human myelogenous leukemic cell lines, HL-60 and U-937, induced by either macrophage culture supernatant or retinoic acid. The decline of asparagine synthetase activity closely paralleled the expression of various maturation markers, but could also be induced by serum starvation. These results suggest that asparagine synthetase or L-asparagine has some biological function in growth regulation of these leukemia cell lines.     

Alteration in insulin receptor expression accompanying differentiation of HL-60 leukemia cells

Differentiation of leukemic cells in vitro is characterized by the sequential appearance of morphological, functional, and biochemical markers of maturation. The interaction of insulin with its receptor may be a regulator of growth and differentiation of leukemic cells. Human promyelocytic leukemia cells (HL-60) demonstrate specific reversible insulin binding consistent with properties of human insulin receptor. HL-60 cells treated with 500 microM N6,O2-dibutyryl adenosine 3',5'-cyclic monophosphate, 1 microM 1 alpha, 25-dihydroxyvitamin D3, or 41 nM phorbol-12-myristate-13-acetate expressed monocytic markers of differentiation and an increase in insulin receptor expression. The change in insulin receptor expression with 1 microM 1 alpha, 25-dihydroxyvitamin D3 and N6,O2-dibutyryl adenosine 3',5'-cyclic monophosphate induction was further characterized by Scatchard analysis. High affinity binding (Kd) constant was not altered, and the change in binding was attributed to receptor number. Commitment to increased insulin receptor expression was demonstrated after 1-h exposure to 1 microM 1 alpha, 25-dihydroxyvitamin D3. Agents which induced granulocytic differentiation, such as 160 mM dimethyl sulfoxide and 100 nM retinoic acid, significantly decreased insulin receptor expression compared to monocytic inducing agents. This difference in insulin receptor expression correlated with binding characteristics in normal human peripheral granulocyte and monocytes. The HL-60 cell line offers a model for the study of the molecular events which lead to the contrasting insulin receptor expression during myeloid and monocytoid hematopoiesis.     

Establishment, characterization and differentiation induction of a new human diploid myelomonocytic cell line (HL-92) derived from a patient with acute myelomonocytic leukemia

With very few exceptions, it has not been possible to grow human myeloid cells for long periods in culture. We have recently developed techniques enabling the long-term in vitro propagation of normal immature myeloid cells from fresh foetal cord blood and monocytes from normal adult peripheral blood, and have utilized these procedures to initiate cultures of fresh peripheral blood leukocytes from leukemic donors. In four of 26 leukemic samples tested, leukocyte replication beyond that obtained in control cultures was observed, and in one of these HL-92, derived from the peripheral blood of a patient with acute myelomonocytic leukemia, the culture has continued to replicate slowly for over 2 years under the special growth conditions. Morphological, cytochemical, immunological and functional studies show that the culture consists predominantly of immature myeloid cells (myeloblasts through to myelocytes) but also contains some mature neutrophils and monocytes. At least a portion of HL-92 cells express Fc and complement receptors, contain histocompatability locus antigens, including HLA-DR, and release GM-CSA, low levels of PGE and lysozyme. HL-92 cells can be induced with DMSO or RA to differentiate into mature neutrophils (an increase from 20 to 70% of the cell population) as determined by morphology, by an increase in phagocytic cells, and superoxide anion production. Fresh leukocytes from the patient's bone marrow appeared to have a diploid karyotype. However a consistent chromosomal abnormality observed in HL-92 was a deletion in the long arm of chromosome 11 [del(11)(q23)]. This is consistent with recent observations in monocytic leukemia. Since the few other established human myeloid cell lines have various chromosomal abnormalities, and some respond to differentiation inducers, while others do not, there appears to be no detectable common chromosome change required either for in vitro growth of myeloid cells or their response to inducers of differentiation. These cell lines and the application of the techniques described here for the growth of myeloid cells from other leukemic or normal sources should be helpful in the study of normal and leukemic myeloid cell growth and differentiation.     

Treatment of human promyelocytic leukemia in the SCID mouse model with cotylenin A,an inducer of myelomonocytic differentiation of leukemia cells

Cotylenin A has differentiation-inducing activity in human myeloid leukemia cell lines and leukemic cells that were freshly isolated from acute myeloid leukemia (AML) patients in primary culture. Injection of the human promyelocytic leukemia cell line NB4 into SCID mice resulted in the death of all mice due to leukemia. Administration of cotylenin A significantly prolonged the survival of mice inoculated with NB4 cells. In an in vivo analysis, cotylenin A induced the differentiation of leukemia cells in a retinoid-resistant leukemia model. Cotylenin A may be useful for differentiation therapy of retinoid-resistant leukemia.     

Production by undifferentiated myeloid leukemia cells of a novel growth-inhibitory factor(s) for partially differentiated myeloid leukemic cells

Mouse monocytic Mm-A cell line is a highly leukemogenic variant cell line of the monocytic and non-leukemogenic Mm-1 cell line, which developed spontaneously from mouse myeloid leukemia M1 cells. Growth-inhibitory factor (GI factor) for Mm-A cells was found in conditioned medium (CM) of differentiation inducer-resistant myeloblastic M1 cells (clone R-1). The R-1 cells were cultured with or without 2% calf serum for 2 days, and the CM was fractionated with 50% ammonium sulfate and used as the GI factor preparation (termed R1CM). When Mm-A cells were cultured with 5% (v/v) R1CM for 3 days, their growth was inhibited about 80%. This inhibition of Mm-A cell growth by R1CM was irreversible. This GI factor also inhibited the growth of M1 cells that had been pretreated with inducer and had expressed some differentiation-associated properties but still retained a proliferative capacity. In contrast, it scarcely inhibited the growth of untreated M1 cells. The GI factor inhibited the growth of other mouse monomyeloblastic leukemic WEHI-3B D+ cells pretreated with a differentiation inducer, retinoic acid, and mouse monocytic leukemia J774.1 cells. However, it did not affect the growth of human monocytic (U937 and THP-1) or myeloid (KG-1, ML-1, and HL-60) cell lines. These results suggest that GI factor produced by parent myeloblastic and inducer-resistant M1 cells preferentially inhibits the growth of mouse monocytic leukemia cells in intermediate stages of differentiation from myeloblastic leukemia cells to mature macrophages.     

Induction of morphological and functional differentiation of human promyelocytic leukemia cells (HL-60) by componuds which induce differentiation of murine leukemia cells

Various compounds active in promoting in vitro differentiation of certain murine leukemia cell lines (Friend erythroleukemia cells and mouse myeloid leukemia cells) were tested for their capacity to induce differentiation of HL-60 cells, a human promyelocytic leukemia cell line capable of terminally differentiating in vitro to functionally mature granulocytes. Polar planar compounds including hexamethylene bisacetamide (HMBA), certain purines (particularly hypoxanthine), and actinomycin-D induced morphological and functional (as assessed by the capacity to reduce NBT dye) differentiation of HL-60. In contrast, hemin, ouabain, prostaglandin E1, X-irradiation, dexamethasone and some other anti-leukemic chemotherapeutic agents induced little if any significant differentiation of HL-60 cells. These results, together with previous observations with murine leukemia cells, suggest that the human HL-60 cells share common cellular target sites for the inducing action of polar planar compounds, hypoxanthine and actinomycin-D with some murine leukemic cells. In contrast, hemin, ouabain and prostaglandin E1 may be specific for mouse erythroleukemia cells, while X-irradiation and chemotherapeutic agents induce differentiation of both types (erythroid and myeloid) of mouse leukemic cells, but have little effect on HL-60 cells.     

Diversity of acute non-lymphocytic leukemia analyzed with monoclonal antibodies reactive with myeloid differentiation antigens

The expression of myeloid differentiation antigens on acute nonlymphocytic leukemia cells (ANLL) was analyzed with four distinctive monoclonal antibodies (MoAbs); YM-1, HL-1, 20.2 and 20.3. These four MoAbs were shown to recognize different stages of differentiation of myeloid progenitor cells (CFU-GM) and/or mature myeloid cells. Consequently, leukemia cells of 68 adult patients with ANLL were able to be divided into four groups according to their expression of the antigens defined by these MoAbs: group 1 HL-1(-), YM-1(-), 20.2(-), 20.3(-) (13 cases); group 2 HL-1(+), YM-1(-), 20.2(-), 20.3(-) (16 cases); group 3 HL-1(+), YM-1(+), 20.2(-), 20.3(-) (13 cases) and group 4 HL-1(+), YM-1/20.2/20.3(+/(-)) (26 cases). This classification elucidated not only the maturation stages of ANLL but also the diversity of ANLL. When compared with the morphological classification, acute myeloblastic leukemia (AML) cases (M1 and M2 of the FAB classification) were evenly distributed among all four groups. These data suggest that the AML group was composed of heterogeneous leukemias which expressed surface phenotypes of different maturation stages ranging from the most immature stage to the mature stage. In contrast, the mature type (group 4) was composed of not only AML (M1 and M2), but also acute monocytic leukemia (M4) and acute myelomonocytic leukemia (M5). The clinical courses of these 68 patients revealed that the complete remission rate, remission duration and survival time were not significantly different among the four groups.     

Translational study of vitamin D differentiation therapy of myeloid leukemia: effects of the combination with a p38 MAPK inhibitor and an antioxidant.

Human myeloid leukemia cell lines are induced to terminal differentiation into monocyte lineage by 1,25-dihydroxyvitamin D3 (1,25D3) or its analogs (deltanoids). However, translation of these findings to the clinic is limited by calcemic effects of deltanoids. Strategies to overcome this problem include combination of deltanoids with other compounds to induce differentiation at lower, noncalcemic, deltanoid concentrations. We previously showed that either carnosic acid, an antioxidant, or SB202190, a p38 MAPK inhibitor, increase the potency of 1,25D3 in the HL60 cell line. Here, we report that simultaneous addition of both these agents further increases differentiation potency of deltanoids in this cell line and in freshly obtained leukemic cells ex vivo. Activity of MAPK pathways showed that increased differentiation was associated with enhanced activity of JNK pathway in all responding cell subtypes. Our studies suggest that patients with CML or AML subtypes M2 and M4, but not M1, M3 or M4eo, are particularly suitable for this combination therapy. We conclude that the established cell line HL60 presents a good model for some, but not all, subtypes of myeloid leukemia, and that the JNK pathway plays an important role in monocytic differentiation of human leukemic cells ex vivo, as well as in vitro.     

Induction of insulin receptor expression of human leukemic cells by 1 alpha, 25 dihydroxyvitamin D3

The HL-60 and U-937 leukemic cell line and explants of fresh human leukemia cells were differentiated in vitro by incubation with 1 alpha, 25 dihydroxyvitamin D3 (Vit D). Morphologic change to monocytes was demonstrated in the promyelocytic (HL-60) line but not in the U-937 line and four of five leukemic cells. One patient with chronic granulocytic leukemia in the myeloid blast phase had incomplete morphologic change with Vit D treatment. In all cells studied, an increase in specific insulin receptor binding was independent of morphologic maturation. An increase in insulin receptor expression by Vit D was an early monocytic membrane marker dissociated from morphologic and functional alterations.     

Effects of transforming growth factor-beta and activin A on vitamin D3-induced monocytic differentiation of myeloid leukemia cells

We examined the effects of transforming growth factors beta(TGF-beta) alone and in combination with 1 alpha,25-dihydroxyvitamin D3 (VD3) on human leukemic cell lines (HEL/S, HL-60 and K562). TGF-beta 1 alone at higher concentrations induced monocytic differentiation of HEL/S cells. Combinations of TGF-beta 1 and VD3 synergistically inhibited cell proliferation and induced monocytic differentiation of HEL/S and HL-60 cells. TGF-beta 2 (a subtype of TGF-beta) and erythroid differentiation factor (EDF/Activin A, a member of the TGF-beta gene family) also inhibited growth and induced monocytic differentiation of HL-60 cells in synergy with VD3. Thus combinations of VD3 and TGF-beta (TGF-beta 1, -beta 2, or EDF) acted synergistically in inhibiting cell proliferation and inducing monocytic differentiation of human leukemia cells.     

Expression of c-kit Receptor (CD 117) and CD34 in Leukemic Cells

The expression of c-kit receptor (c-kit R; CD117) and CD34 was examined in acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), chronic myeloid leukemia (CML) in blastic transformation (BT), and myelofibrosis (MF) in myeloid BT. In myeloid leukemia including AML, CML-myeloid BT and MF-myeloid BT, both c-kit R and CD34 were expressed synchronously, while in lymphoid leukemia including ALL and CML-lymphoid BT, only CD34 was highly expressed. A close correlation between c-kit R and CD33 expression and an inverse correlation between c-kit R and CD 19 expression were observed when all of the myeloid plus lymphoid leukemia cells were analysed. There was a close correlation between c-kit R and CD34 expression in the myeloid leukemia cells, c-kit R expression may be associated with myeloid phenotypes of leukemic cells and may be useful for the diagnosis of myeloid leukemia. The literature of c-kit R expression in leukemic cells is reviewed here and the comparison of c-kit R and CD34 expression in normal hematopoietic progenitor cells with those on the leukemic counterparts was discussed.     

Glycosyltransferase activities in leukemic cells from patients and human leukemic cell lines

The cell membrane fraction from c-ALL, B-ALL, Ph′+ ALL, B-CLL, T-CLL, AML, blastic-CML, normal leukocytes, PHA-stimulated lymphocytes and several T, B and myeloid human leukemic cell lines has been used in different cell types to demonstrate different patterns of glycosyltransferase activity. Both B- and T-CLL cell membranes have low fucosyltransferase B and A activity compared to acute leukemias; while sialyltransferase activity is higher in B- than in T-CLL. AML cell membranes and ML-1 human myeloblast cell line membranes have exceptionally high fucosyltransferase A activity compared to all other leukemic cells or cell lines. Human leukemic B cell lines expressed cell membrane sialyltransferase, fucosyltransferase B and probably fucosyltransferase A activity several times higher than T cell lines. Human myeloid cell lines ML-1 and HL-60 express 5- to 20-fold higher galactosyltransferase activity than human leukemic T and B cell lines. Both sialyltransferase and galactosyltransferase activity were higher in all leukemic cells than in normal leukocytes and PHA-stimulated normal lymphocytes. This is the first study carried out on glycosyltransferases using cells obtained from leukemic patients characterized immunologically. These results indicate that all glycosyltransferase activity, with the exception of fucosyl-transferase activity in CLL, were higher in leukemic cells than in normal cells. Moreover, large differences in these enzymes, e.g. very high galactosyltransferase activity in myeloid cell lines compared to B and T cell lines, of fucosyltransferase A in AML and myeloblast cell lines compared to all other cells, and of sialyltransferase in B-CLL or B cell lines compared to T-CLL or T cell lines, could be useful in characterizing certain leukemias and hematopoietic cell lines.