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At least 19 recordsLinked to original sources
PubMed1981

Molecular weight analysis of Fc gamma-binding proteins of lymphoid leukemia, myeloid leukemia, and hairy-cell leukemia.

The molecular weights of EDTA-mercaptoethanol-soluble Fc gamma-affined proteins isolated from chronic lymphocytic leukemia of the B type, prolymphocytic leukemia of the B type, chronic myeloid leukemia and hairy-cell leukemia were compared. SDS polyacrylamide gel electrophoresis of the Fc gamma-binding material obtained from all six cases of B type leukemia revealed a single peak with an apparent molecular weight of 28,000. The Fc gamma-affined material isolated from the cells of two cases of chronic myeloid leukemia showed two peaks, one with an apparent molecular weight of 42,600 and one with an apparent molecular weight of 18,800. The Fc gamma-affined material isolated from the cells of two cases of hairy-cell leukemia electrophoresed in the form of a closely spaced double peak. One component of the double peak had an apparent molecular weight of 28,000 and thus corresponds to the Fc gamma-binding material of leukemic B cells. The second component had a slightly lower molecular weight. The latter component is not present on either leukemic B cells or myeloid cells. The results indicate that the EDTA-mercaptoethanol-soluble Fc gamma-affined proteins of different types of cells differ in molecular weight, and thus in molecular structure.

B-Lymphocytes↗
PubMed1989

Differentiation-inducing effect of recombinant human tumor necrosis factor alpha and gamma-interferon in vitro on blast cells from patients with acute myeloid leukemia and myeloid blast crisis of chronic myeloid leukemia.

Tumor necrosis factor alpha (TNF-alpha) and gamma-interferon (IFN-gamma) have been shown to suppress clonogenic growth in cultures containing blast cells obtained from patients with acute myeloid leukemia. We report that recombinant human TNF-alpha and IFN-gamma are also able to induce functional and morphological maturation in fresh myeloid leukemic cells in vitro. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (11 patients) or myeloid blast crisis of chronic myeloid leukemia (5 patients), it was found that recombinant human TNF-alpha and IFN-gamma significantly enhanced the number of cells reducing nitroblue tetrazolium, as compared to control cultures containing no cytokine (P less than 0.001 and P less than 0.001, respectively). Cells from responders showed alterations characteristic of monocyte/macrophage differentiation, adherence to plastic surfaces, development of positive staining for alpha-naphthyl acetate esterase, typical morphology, and expression of cell surface antigens detected by the monoclonal antibodies Mo-1, Mo-2, and My-4. Both cytokines decreased the number of viable cells, the number of blast cells, and the number of cluster-forming units in suspension culture, suggesting inhibitory actions on the growth capacity of leukemic cells. Compared to the maximum effects of either factor alone, the combination of recombinant human TNF-alpha and IFN-gamma significantly increased the extent of growth inhibition and cell adherence but did not result in further increases in nitroblue tetrazolium reduction. The presence of Auer rods in IFN-gamma or TNF-alpha differentiation-induced macrophages with cells from a patient with M5 acute myeloid leukemia demonstrates that these cytokines can induce differentiation of a leukemic clone in primary cells from patients with leukemia.

Adolescent↗
PubMed1992

Role of hemopoietic growth factors in the development and suppression of myeloid leukemia.

Myeloid leukemia development requires the acquisition by a cell of two abnormalities: an abnormal capacity for self-replication; and a capacity for autocrine stimulation, usually involving the known growth factors for granulocyte-macrophage cells. Curiously, in human leukemia, this does not usually result in autonomous growth when assessed in clonal in vitro cultures. Depending on gene programming, in particular in human or murine myeloid leukemias, the hemopoietic growth factors can also suppress the leukemic population by inhibiting the capacity of the leukemic stem cells for self-generation. The regulator showing the highest suppressive activity varies from leukemia to leukemia, with G-CSF. GM-CSF, IL-6, or leukemia-inhibitory factor (LIF) all having high activity on appropriate target cells. Combinations of these regulators are more effective than single agents alone. Analyses of human HL60, U937 and murine M1 leukemic models indicate that the development of morphological maturation in the leukemic cells is not a necessary feature of stem-cell suppression. LIF has an anomalous action on stem-cell self-generation, being highly effective in the suppression of certain myeloid leukemic cell lines, but being necessary to maintain self-generation in normal embryonic cells. This suggests the existence of a common control medium governing self-generation decisions in cells of different lineages, but that the outcome of the decision is determined by the differentiation program operating in different cells. The colony-stimulating factors are being used in combination with chemotherapy in the treatment of patients with acute myeloid leukemia, but the above principles require caution in certain situations.

Granulocyte-Macrophage Colony-Stimulating Factor↗
PubMed1991

Growth regulation of malignant clonogenic cells in acute myeloid leukemia.

Myeloid leukemic progenitor cells proliferate in vitro in response to a variety of humoral factors, the most prominent among these being granulocyte-macrophage colony-stimulating factor (GM-CSF). The mechanism by which GM-CSF transduces its proliferative signal in acute myeloid leukemia has been extensively investigated over the past year. It is now known that the GM-CSF belongs to a new family of hematopoietic growth factor binding proteins which are characterized by a relatively short intracytoplasmic domain that lacks a tyrosine kinase sequence. Nevertheless, studies performed using GM-CSF-dependent leukemic cell lines demonstrate the appearance of several new phosphotyrosine species after GM-CSF exposure, suggesting that receptor activation is directly or indirectly linked to tyrosine kinase stimulation. Apart from the basic biology of GM-CSF-induced signal transduction, the ability of this factor to enhance the S-phase fraction of myeloid leukemia blasts may have important therapeutic implications. Clinical trials are currently being conducted in an attempt to determine whether GM-CSF is able to overcome kinetic resistance of leukemic myeloblasts to cell cycle-specific agents such as cytarabine in the treatment of patients with acute myeloid leukemia.

Clone Cells↗
PubMed1983

Use of monoclonal antibodies as a diagnostic tool in human leukemia. I. Acute myeloid leukemia and acute phase of chronic myeloid leukemia.

Various monoclonal antibodies (mAbs) detecting certain different epitopes on myeloid cells (VIMD5, D5 D6, OKM1, Leu-M3, VIEG4, OKIa 1) have been used in combination with conventional markers (antihuman myeloid hetero-antiserum, FcIgG-receptors, C3d-receptors) to further define the phenotypic heterogeneity of myeloid leukemia. Subsequent leukemic samples from previously untreated patients with acute myeloid leukemia (AML) (51 adults, 24 children) and from nine adult patients in the acute phase of chronic myeloid leukemia (CML-BC) were studied. It was possible to demonstrate quantitative differences in the expression of antigens on the various leukemia subtypes which could be exploited for diagnosis. Furthermore our results revealed that there is a very close correlation between the different surface phenotypes and the types morphologically assessed according to FAB-criteria.

Adult↗
PubMed2001

[Antisense oligodeoxynucleotide of telomerase gene enhances cisplatin-induced apoptosis in acute myeloid leukemia and chronic myeloid leukemia cells].

OBJECTIVE: To explore the effect of human telomerase reverse transcriptase(hTERT) gene antisense oligodeoxynucleotide (ASODN) on cisplatin-induced apoptosis in cultured primary acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cells. METHODS: Cell surviving fraction was determined using the trypan blue dye exclusion assay. Apoptosis was detected by DNA gel electrophoresis and flow cytomertric cell cycle analysis. RESULTS: Treatment with cisplatin after 24 hours of exposure of the cells to ASODN significantly reduced the number of viable AML and CML cells. However, there was no difference on AML and CML cells survival between those treated with sense oligodeoxynucleotide (SODN)/cisplatin combination and cisplatin alone. Agarose gel electrophoresis of genomic DNA from the blasts of AML and CML treated with ASODN and cisplatin combination for 72 hours showed typical DNA "ladder", but DNA from AML or CML cells treated with SODN plus cisplatin or cisplatin alone did not. The percentage of apoptotic AML and CML cells treated with cisplatin for 48 or 72 hours after 24 hours of exposure to ASODN (42.68%, 35.72%) was significantly different with that of apoptotic cells treated with SODN plus cisplatin (29.02%, 23.84%) or cisplatin alone (27.53%, 21.02%). CONCLUSION: hTERT ASODN could enhance the cisplatin-induced apoptosis of AML and CML cells.

Acute Disease↗
PubMed2000

Different immune reconstitution in multiple myeloma, chronic myeloid leukemia and acute myeloid leukemia patients after allogeneic transplantation of peripheral blood stem cells.

In this study we compared the lymphocyte reconstitution in 13 multiple myeloma (MM), nine acute myeloid leukemia (AML) and 10 chronic myeloid leukemia (CML) patients after allogeneic G-CSF-mobilized PBSC transplantation from HLA-identical siblings. Conditioning regimens included standard total body irradiation + cyclophosphamide (CY), or busulphan + CY, whereas VP-16 was added in patients with advanced disease. Overall comparable numbers of mononuclear cells, CD34+ cells and CD3+ T cells were infused in each group. A significantly higher CD3+ T cell number was observed in MM and AML than in CML patients 1 month after transplant. However, MM patients showed a faster and better recovery of CD4+ T cells than both AML and CML patients at 3 months (P = 0.01 and P = 0.01, respectively) and 12 months (P = 0.01 vs AML, while P = NS vs CML) after transplant, and had a CD4:CD8 ratio > 1 with a median CD4+ T cell value > 400/microl 1 year after transplant. Development of acute graft-versus-host disease (GVHD) did not affect CD4:CD8 ratios but patients who experienced acute GVHD > grade I had lower CD4+ and CD8+ T cell numbers at all time points. However, after excluding patients with GVHD > grade I, MM patients still showed a significantly higher CD4+ T cell value than patients with myeloproliferative diseases 1 year after transplant. These findings suggest that although allogeneic PBSC transplantation induces rapid immune reconstitution, different kinetics may occur among patients with hematological malignancies. In particular, the rapid reconstitution of CD4+ T cells in MM patients may contribute to the low transplant-related mortality achieved in this disease.

Acute Disease↗
PubMed2005

The incidence of submicroscopic deletions in reciprocal translocations is similar in acute myeloid leukemia, BCR-ABL positive acute lymphoblastic leukemia, and chronic myeloid leukemia.

We compared the incidence of submicroscopic deletions accompanying balanced translocations using interphase fluorescence in situ hybridization (FISH) in 245 patients with chronic myeloid leukemia (CML), 79 patients with acute lymphoblastic leukemia (ALL) and BCR-ABL (n=70) or MLL rearrangements (n=29), and 412 patients with acute myeloid leukemia (AML) with CBFB-MYH11 (n=122), PML-RARalpha (n=108), AML1-ETO (n=112), or MLL rearrangements (n=98). The incidence of submicroscopic deletions was 2-9% depending on the entity.

Acute Disease↗
PubMed2001

High-dose cytosine arabinoside and idarubicin treatment of chronic myeloid leukemia in myeloid blast crisis.

Chronic myeloid leukemia in myeloid blast crisis (CML-MBC) is highly resistant to standard induction chemotherapy regimens. Anecdotal results from previous clinical trials support the concept of dose escalation in patients with CML-MBC. Eight patients with CML-MBC were treated with cytosine arabinoside (Ara-C) 1.5-3.0 g/m2 intravenously over 1 hr every 12 hr for 12 doses and idarubicin 12 mg/m2 intravenously daily for 3 days. Sixteen previous reports describing the use of Ara-C-based chemotherapy regimens in patients with CML-MBC were also reviewed. Our patients' median age was 62 years (range, 42-69 years). One patient achieved complete hematologic remission (95% confidence interval, 0.3%, 53%). The median survival for our patients was 7.3 months. These results were not different from previous published reports using Ara-C-based chemotherapy regimens to treat CML-MBC. In summary, the combination of high-dose Ara-C and idarubicin did not improve the overall prognosis of patients with CML-MBC. Innovative approaches need to be explored for this patient population.

Adult↗
PubMed1989

Concomitant chronic lymphocytic leukemia, acute myeloid leukemia, and thrombosis with protein C deficiency. Case report and review of the literature.

A patient is reported who presented simultaneously with two distinct forms of leukemia: chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). The diagnosis of CLL was supported by the presence of lymphocytosis, lymphadenopathy, and splenomegaly with mature B-cell markers on the population of lymphoid cells in the bone marrow. AML was documented by the presence of circulating blast cells and 50% blasts with myeloid markers and Auer rods in the bone marrow. A complete remission from both forms of leukemia was obtained after treatment for the AML. The patient also experienced the temporal occurrence of venous thrombosis for the first time at the age of 69 years, shortly before the diagnosis of leukemia. Protein C deficiency was documented and may have been hereditary as suggested by the strong family history of thrombosis or alternatively may have been the consequence of one of the leukemias.

Aged↗
PubMed2004

Gemtuzumab ozogamicin for relapsed and refractory acute myeloid leukemia and myeloid sarcomas.

Antibody-targeted chemotherapy is a promising approach in patients with hematological malignancies. In particular, gemtuzumab ozogamicin (GO, formerly CMA-676), an anti-CD33 antibody linked to calicheamicin, has been approved for the treatment of elderly patients with acute myeloid leukemia (AML) in relapse. Nevertheless, no data are until now available concerning the possible efficacy of GO for myeloid sarcomas (MS). We treated with GO 24 AML patients, in 5 cases presenting with myeloid sarcomas of the skin or bones. The overall complete response rate was 21%. The median duration of response was 6 months. Four out of the 5 patients with myeloid sarcoma showed a regression of the masses, in two cases also obtaining a clearance of marrow blasts. The most common adverse events included thrombocytopenia, neutropenia, infections, elevation of bilirubin and hepatic transaminases. Notably, severe bleeding occurred in 5 cases (21%). VOD was documented in 1 case. We conclude that GO is effective as a single agent in AML and myeloid sarcomas. Further data are required to clarify the possible correlation between GO administration and occurrence of bleeding.

Adult↗
PubMed1995

Acute monocytic leukemia: a myeloid leukemia subset that may be sensitive to methotrexate.

Impaired polyglutamylation of methotrexate (MTX) and thus poor retention is believed to be the basis of intrinsic resistance in blasts from patients with acute myeloid leukemia (AML) to MTX. We studied additional samples from patients with this disease, and confirmed that polyglutamylation of MTX was poor in ANLL blast cells. However, in one subset of ANLL, acute monocytic leukemia, (M5) leukemia blasts were found to be capable of accumulating and forming long-chain MTX polyglutamates. An acute monocytic leukemia cell line, THP-1 also was found to accumulate high levels of MTX polyglutamates and was relatively sensitive to MTX, strengthening the concept that M5 blasts may be sensitive to this drug. MTX may be an overlooked drug for the treatment of acute monocytic leukemia.

Adult↗
PubMed2006

Increased cellular glutathione and protection by bone marrow stromal cells account for the resistance of non-acute promylocytic leukemia acute myeloid leukemia cells to arsenic trioxide in vivo.

Arsenic trioxide (ATO) is a novel agent for acute promylocytic leukemia (APL). Studies performed in vitro have demonstrated that ATO also induces cell-cycle arrest and apoptosis in multiple cancers, including non-APL acute myeloid leukemia (AML). To explore the potential use of ATO on non-APL AML, we treated the leukemic cells in vivo using a NOD/SCID animal model. Mice harboring HL-60 or NB-4 leukemia or primary AML-M2 cells were treated daily with 5 mug/g ATO intraperitoneally for a maximum of 6 weeks. Although ATO initially appeared to be effective on HL-60 cells, it failed to decrease the leukemic cells in bone marrow (BM) after the extended treatment (52.2 +/- 10.7% vs. 62.2 +/- 2.6% in the controls; P = 0.51); whereas the same treatment to NB-4 leukemic mice significantly decreased the percentage of leukemic cells in BM. ATO also failed to eradicate the primary AML cells in vivo. The reason for the treatment failure was that HL-60 cells quickly developed resistance in vivo. The drug resistance could be partly attributable to the increase of cellular glutathione as a result of compensatory response to ATO treatment because depletion of glutathione with buthionine sulfoximine reversed the drug resistance in vitro. Meanwhile, BM stromal cells also contributed to the drug resistance. Leukemic cells grown on an adherent layer of MS-5 stromal cells in the presence of ATO were more proliferative and less apoptotic and had increased expression cyclin D1, Bcl-xL and Bcl-2 and decreased expression of p21, likely protecting the leukemic cells from ATO cytotoxicity. Therefore, our study suggests that strategies to inhibit the compensatory increase of glutathione and block the interaction between leukemic cells and BM stromal cells should be employed before applying ATO to non-APL hematologic malignancies.

Acute Disease↗
PubMed1986

[Bone marrow transplantation in acute leukemia, chronic myeloid leukemia, severe aplastic anemia and stage IV neuroblastoma. Effect of antiviral prevention with anti-CMV-hyperimmunoglobulin and acyclovir].

Bone marrow transplantation was performed between IV/82 and X/85 in 64 patients with acute leukemia (n = 36), chronic myelogenous leukemia (CML; n = 13), severe aplastic anemia (n = 12), and neuroblastoma stage IV (n = 3). Of these patients 57 received allogeneic marrow from HLA-ABCDR identical, MLC-negative sibling donors. Six transplants were performed with syngenic marrow and one with autologous marrow. Of the 64 patients 48 survived 40-1,250 days after transplantation, resulting in a survival rate (SR) of 75% and a survival probability (SP) of 71%. Of the 36 patients suffering from acute leukemia (SR = 64%, SP = 51%), patients with acute myelogenous leukemia (AML) in first complete remission (n = 11; SR = 81%, SP = 76%), as well as patients with acute lymphatic leukemia (ALL) in 1st to 4th complete remission at the time of transplantation (n = 14; SR = 81%, SP = 76%) show a favorable prognosis. A poor survival rate was seen for patients with AML when transplanted in second or partial remission (1/5; SR = 20%), as well as for patients suffering from ALL and transplanted during relapse or partial remission (1/6; SR = 16%). Of 13 patients suffering from CML 12 survived the transplantation free of relapse (SR = 93%, SP = 92%), and one patient died from varicella zoster pneumonia. Of the transplanted patients with severe aplastic anemia, 12 of 13 are surviving with complete hematologic reconstitution; one patient, however, died on day 10 from a sepsis. In our patient group, the SR as well as the SP has been improved through changes in the irradiation protocol concomitant with prophylactic application of anti-CMV hypergammaglobulin, as well as through additional oral medication of Azyklovir. The 41 patients (BMT No. 7-47) with total body irradiation at one time show an SR of 44% and an SP of 41%. The following 46 patients (BMT No. 48-93) have reached an SR of 83% and an SP of 74% under the regimen of fractionated total body irradiation, plus prophylaxis with anti-CMV hypergammaglobulin and Azyklovir. Within this group, no fatal CMV pneumonia was encountered as opposed to six patients lost from CMV pneumonia in the first group.

Acyclovir↗
PubMed1999

Regulation of c-fos gene transcription and myeloid cell differentiation by acute myeloid leukemia 1 and acute myeloid leukemia-MTG8, a chimeric leukemogenic derivative of acute myeloid leukemia 1.

Both acute myeloid leukemia 1 and c-Fos are regulatory factors of hematopoietic cell differentiation. We identified that the c-fos promoter contains an acute myeloid leukemia 1 binding site at nucleotide positions -6-+14. c-fos promoter activity was induced by transient overexpression of acute myeloid leukemia 1 in Jurkat T-cells, but not by that of the short form of acute myeloid leukemia 1-MTG8, a chimeric acute myeloid leukemia 1 protein. In 32Dcl3 myeloid cells, stable overexpression of acute myeloid leukemia 1-MTG8 blocked the c-fos gene transcription and cell differentiation, but that of acute myeloid leukemia did not. These data suggest that acute myeloid leukemia 1 and acute myeloid leukemia 1-MTG8 reciprocally regulate the myeloid cell differentiation, possibly by the way of regulating c-fos gene transcription.

Cell Differentiation↗
PubMed2004

Modern diagnostics in chronic myeloproliferative diseases (CMPDs).

According to the new WHO classification a group of chronic myeloproliferative diseases (CMPDs) were defined: chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia and hypereosinophilic syndrome (CEL/HES), polycythemia vera (PV), chronic idiopathic myelofibrosis (with extramedullary hematopoiesis, CIMF), essential thrombocythemia (ET), and so called CMPD/unclassifiable. As clinical features and laboratory findings differ widely between these diseases several diagnostic approaches are mandatory at diagnosis for classification and are needed also for follow up studies, especially for the measurement of minimal residual disease (MRD). We here outline the laboratory set up at diagnosis and during follow up in CMPDs with specific focus on the respective therapeutical consequences. Only by using a comprehensive diagnostic panel including cytomorphology, cytogenetics, and molecular genetic methods establishing the correct diagnosis, optimizing treatment as well as evaluating treatment response is possible in CMPDs today.

Blood Cell Count↗
PubMed1999

Trisomy 22 in acute myeloid leukemia: a marker for myeloid leukemia with monocytic features and cytogenetically cryptic inversion 16.

Trisomy 22 is an uncommon chromosomal abnormality in acute myeloid leukemia. Recent studies, however, have shown an association between trisomy 22 and acute myeloid leukemia with a monocytic component, and in particular, acute myelomonocytic leukemia with marrow eosinophilia. Furthermore, it has also been suggested that trisomy 22 was in fact only a secondary chromosomal change occurring in acute myeloid leukemia with inv(16). In this report, we analyze the morphological, cytogenetic, and molecular findings of three cases of acute myeloid leukemia with trisomy 22 but without cytogenetic evidence of inv(16). The results indicate a consistent association between trisomy 22 and inv(16), the latter being cytogenetically cryptic in some cases. This finding is of potential diagnostic and therapeutic significance.

Acute Disease↗