|
1. |
Immature and Differentiated Neoplastic Populations in Acute Lymphoid Leukemia of Childhood: Biological and Clinical Implications |
|
Leukemia&Lymphoma,
Volume 11,
Issue 1-2,
1993,
Page 1-7
EstrovZeev,
ReGian Guldo,
ZipfTheodore F.,
Preview
|
PDF (905KB)
|
|
摘要:
Despite significant improvement in the therapy for acute lymphoid leukemia (ALL) of childhood, approximately 30% of patients relapse. Unfortunately, since no successful treatment for recurrent disease has been developed, the majority of these patients die. Recently, we presented evidence consistent with the presence of a limited program of differentiation in B-precursor ALL that is reminiscent of normal B-cell development. We found that ALL cell populations consist of both a subpopulation of progenitors with the immunophenotype of normal B-cell precursors that has self-renewal capability and a second subpopulation with a more mature early B-cell immunophenotype that is without self-renewal capability but can proliferate to a limited extent. In our recent studies we were able to grow the progenitor cells in the ALL blast colony assay and establish their leukemic origin using the polymerase chain reaction. Our results suggest that these progenitors are the cells that sustain the disease. We hypothesize that these cells may remain quiescent, for a time, and either eventually die or regain proliferative capability and cause relapse. Further studies aimed both at detecting residual ALL and determining changes in their biology may provide an understanding of the mechanisms of relapse in this disease.
ISSN:1042-8194
DOI:10.3109/10428199309054724
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
|
2. |
A Comparative Analysis of Alkylating Agent and Epipodophyllotoxin-Related Leukemias |
|
Leukemia&Lymphoma,
Volume 11,
Issue 1-2,
1993,
Page 9-13
EllisM.,
RavidM.,
LishnerM.,
Preview
|
PDF (472KB)
|
|
摘要:
This review deals with the differences between leukemias—induced by alkylating agents as opposed to a“new form”of treatment related leukemia due to prior exposure to epipodophyllotoxins the latter having a short treatment—disease onset interval, absence of a MDS phase, a monocytic component and cytogenetic abnormalities involving the 11q23 band. The link between the existence of oncogenes or tumor suppressor genes located on the involved portion of chromosome 11 and the development of epipodophyllotoxin—related leukemia still needs to be examined. Alkylating agents—induced leukemias have a longer treatment—disease onset interval, have a prior myelodysplastic syndrome, and are most frequent myelo-blastic or myelomonocytic in nature. Karyotype analysis reveals partial or complete deletion of chromosomes no. 5 or 7. This form of leukemia is highly resistant to treatment in the majority of cases. Some of the possible molecular mechanisms of leukemogenesis are discussed.
ISSN:1042-8194
DOI:10.3109/10428199309054725
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
|
3. |
Acute Megakaryocytic Leukemia with the t(1;22)(p13;q13 |
|
Leukemia&Lymphoma,
Volume 11,
Issue 1-2,
1993,
Page 15-20
LionThomas,
HaasOskar A.,
Preview
|
PDF (3332KB)
|
|
摘要:
Acute megakaryocytic leukemia (AMKL) was defined as a new subtype of acute non lymphocytic leukemia (ANLL) by the French-American-British (FAB) Cooperative Group in 1985. The first consistent chromosomal anomaly described in this subset of ANLL was the trans-location t(1;22)(p13;q13) which appears to be restricted to this FAB-subtype (FAB-M7) of AML. To our knowledge, 18 AMKL cases with the t(1;22) have been reported until now in the literature. In all instances, the patients were very young children with only one beyond the infant age (12 months) at the time of diagnosis. Based on the results of two reports in which the frequency of this translocation was assessed, the t(1;22) may be estimated to occur in about 30% of pediatric patients with FAB-ANLL subtype M7. In infants with this subset of ANLL, the t(1;22) seems to be present in the majority (>65%) of cases. The detection of this nonrandom chromosomal abnormality may therefore provide an additional diagnostic marker in children with AMKL.Herein we review and discuss the clinical and cytogenetic findings in patients with AMKL and the t(1;22).
ISSN:1042-8194
DOI:10.3109/10428199309054726
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
|
4. |
Mutations of the p53 Gene in B-cell Lymphoma |
|
Leukemia&Lymphoma,
Volume 11,
Issue 1-2,
1993,
Page 21-25
IchikawaAtsushi,
HottaTomomitsu,
SaitoHidehiko,
Preview
|
PDF (449KB)
|
|
摘要:
Mutations of p53 gene have been recognized to be the most common genetic changes in human cancers. Recently, p53 gene mutations have been found in some patients with common subtypes of B-cell lymphoma (9/48:18.8%), Burkitt lymphoma (9/27:33.3%) and chronic lymphocytic leukemia (6/40:15%). Evidences to suggest that p53 gene mutations are associated with the disease progression in B-cell lymphoma have emerged. Functions of wild-type p53 and its mutant's probable role in B-cell lymphomagenesis are described in this review
ISSN:1042-8194
DOI:10.3109/10428199309054727
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
|
5. |
New Insights into the Pathogenesis of Coagulation Dysfunction in Acute Promyelocytic Leukemia |
|
Leukemia&Lymphoma,
Volume 11,
Issue 1-2,
1993,
Page 27-36
TallmanMartin S.,
HakimianDavid,
KwaanHau C.,
RicklesFrederick R.,
Preview
|
PDF (2056KB)
|
|
摘要:
Patients with acute promyelocytic leukemia (APL) are at high risk for the development of life-threatening thrombotic and hemorrhagic complications, particularly during induction chemotherapy. This propensity has been attributed to the release of tissue factor (TF)-like pro-coagulants from the leukemic cells leading to disseminated intravascular coagulation (DIC). However, recent data suggest that the pathogenesis of the coagulopathy is more complicated and may involve activation of the generalized proteolytic cascade resulting in either clotting and/or excessive fibrinolysis. Furthermore, controversy exists regarding the mechanism(s) responsible for the activation of either clotting or fibrinolysis. The malignant promyelocyte may act directly to activate coagulation and/or fibrinolysis. Alternatively, reactive inflammatory cells, which express procoagulant and/or profibrinolytic activities may play an essential role. A third possibility may involve endothelial cell expression of mediators with procoagulant/profibrinolytic properties. Putative profibrinolytic mechanisms include the release of urokinase-type and tissue-type plasminogen activators, decreases in plasminogen activator inhibitor-I and 2, and decreases in alpha-2 plasmin inhibitor. Putative procoagulant mechanisms include the release of tissue factor, Cancer Procoagulant, or cytokines such as interleukin-1, tumor necrosis factor and vascular permeability factor. Putative anticoagulant mediators include annexins, a group of proteins in human tissue which bind phospholipids and have anticoagulant activity, which have been reported in patients with APL. The current treatment of APL is rapidly evolving because of the efficacy of ail-trans retinoic acid (ATRA). All-trans retinoic acid promotes terminal differentiation of leukemic promyelocytes leading to complete remission in the majority of patients with APL with rapid resolution of the coagulopathy. Although the mechanism by which this occurs has not been established, preliminary data suggest that ATRA blocks the down regulation of the thrombomodulin gene and the up-regulation of the tissue factor gene induced by tumor necrosis factor.Since APL is a relatively uncommon disorder, the collaboration of cooperative oncology groups will be important to study patients receiving ATRA or conventional chemotherapy to further elucidate the mechanism(s) of the coagulopathy.The coagulopathy associated with APL is likely a complex interaction of several pathophysiologic processes (Fig. 2). One hypothesis suggests that excessive fibrinolysis mediated by t-PA and/or u-PA from leukemic cells is the predominant process contributing to bleeding in patients with APL. However, the coagulopathy cannot be attributed solely to fibrinolysis, since thrombin generation can be documented in many patients. A second hypothesis proposes that APL-cell derived procoagulants lead to the generation of thrombin, DIC, and bleeding. Still a third hypothesis, suggests that fibrinogenolysis and enzymatic activation and/or destruction of other coagulation factors may be mediated by leukocyte proteases such as elastase. Indirect acting procoagulants derived from leukemic cells, such as IL-I, and/or TNF, may also play an important role via their effects on endothelial cells. The mechanisms leading to bleeding may be heterogenous and may vary among patients. Since APL is a relatively uncommon disorder, the collaboration of cooperative oncology groups will be important to study patients receiving either ATRA or conventional chemotherapy to elucidate further the mechanism(s) of the coagulopathy.
ISSN:1042-8194
DOI:10.3109/10428199309054728
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
|
6. |
Recommended Procedures for the Classification of Acute Leukaemias |
|
Leukemia&Lymphoma,
Volume 11,
Issue 1-2,
1993,
Page 37-50
ScottC. S.,
Den OttolanderG. J.,
SwirskyD.,
PangalisG. A.,
Vives CorronsJ. L.,
de PasqualeA.,
HoveL. Van,
BennettJ. M.,
NambaK.,
FlandrinG.,
LewisS. M.,
PolliackA.,
Preview
|
PDF (8923KB)
|
|
摘要:
The classification of acute leukaemias is now widely based on a combined morphological, cytochemical and immunophenotyping approach. Difficulties are frequently encountered however in reaching an acceptable degree of diagnostic concordance between different laboratories because of variations in the techniques used (in terms of methodologies, reagents and equipment) and diagnostic interpretation. The International Council for Standardization in Haematology (ICSH) convened an expert panel to consider currently available diagnostic techniques with the aim of defining a minimum cytochemical and immunological diagnostic panel that could be used as core components for the classification of acute leukaemia. The proposed ICSH scheme, which attempts to balance the basic requirement for providing precise and informative diagnostic information without limiting its use to only those laboratories with sophisticated facilities, is based on three sequential levels of investigation; primary cytochemistry, intracellular phenotyping and membrane immunophenotyping. The minimum ICSH recommended cytochemistries comprise myeloperoxidase (MPO), chloroacetate esterase (ChlorE) andα-naphthyl acetate esterase (ANAE), and standardised methods for these cytochemistries are detailed in this communication. For cases of acute leukaemia that remain unclassified by primary cytochemistry, subsequent immunological analyses for cytoplasmic CD3, CD22, MPO and nuclear TdT are recommended. The ICSH panel considers that the use of these minimum primary cytochemical and intracellular phenotyping procedures will lead to the consistent classification of most acute leukaemias, and that the third level of investigation (membrane immunophenotyping) should be used for the purposes of confirmation, diagnostic clarification of atypical leukaemias, and the subtyping of acute lymphoblastic leukaemias (ALL). The ICSH panel also recognised that there are a number of additional technologies which can provide definitive diagnostic information, such as cytogenetics and DNA genotyping, but these were excluded from the minimum panel because of their restricted availability. While many specialised laboratories, particularly in the areas of diagnostic research, will continue to use individual investigatory protocols, it is considered that the inclusion of the ICSH scheme as core components would lead to greater consistency when comparing independent studies of acute leukaemia.
ISSN:1042-8194
DOI:10.3109/10428199309054729
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
|
7. |
Phenotypic Characterization of Normal and CML CD34–Positive Cells: Only the Most Primitive CML Progenitors Include Ph-neg Cells |
|
Leukemia&Lymphoma,
Volume 11,
Issue 1-2,
1993,
Page 51-61
de FabritiisPaolo,
DowdingCharles,
BungeyJulie,
ChaseAndrew,
AngusGillian,
SzydloRichard,
GoldmanJohn M.,
Preview
|
PDF (830KB)
|
|
摘要:
We studied the sequence of acquisition of CD33, CD38 and HLA-DR antigens on CD34+ cells from marrow and blood of Ph-chromosome positive CML patients and normal marrow. We examined the Ph status of the various CML cell populations. The mean proportions of normal and CML CD34+ cells expressing CD33 and CD38 were not significantly different. However, a significantly greater proportion of CML CD34+ cells expressed HLA-DR antigens compared with normal CD34+ cells and the level of HLA-DR expression per CML cell was abnormally high. When the sequence of acquisition of these antigens on normal and CML CD34+ cells was evaluated using 3–colour fluorescence analysis, the results suggested that HLA-DR was expressed earlier than CD38 or CD33 and these findings were confirmed by following the acquisition of CD38 and CD34t/DR + /CD38–subpopulation during liquid culture. We performed cytogenetic studies on CD34+ subpopulations in 6 cases. In 4 cases there were some Ph-negative metaphases detectable in the CD34+/DR-subpopulation (range 12.5 to 60%). In the CD34+/DR+ fractions, however, all 6 patients had only Ph-positive metaphases and only 1/5 patients had detectable Ph-negative metaphases in the CD34+/CD38–subpopulation. We conclude that expression of HLA-DR antigens may precede the expression of CD38 on CD34+ cells during normal stem cell differentiation. In CML DR may be expressed aberrantly and Ph-negative cells are found predominantly in the DR negative sub-population.
ISSN:1042-8194
DOI:10.3109/10428199309054730
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
|
8. |
Autoimmune Hemolytic Anemia in Chronic Lymphocytic Leukemia Patients Treated with Fludarabine |
|
Leukemia&Lymphoma,
Volume 11,
Issue 1-2,
1993,
Page 63-68
RamondoFrancesco Di,
GiustolisiRosario,
CacciolaEmma,
O'BrienSusan,
KantarjianHagop,
RobertsonLester B.,
KeatingMichael J.,
Preview
|
PDF (471KB)
|
|
摘要:
Autoimmune hemolytic anemia (AHA) is a frequent complication of chronic lymphocytic leukemia (CLL). Although the pathogenesis of AHA is still unknown, an imbalance of normal residual T cells is believed to play a central role. Since fludarabine is reported to affect primarily T lymphocytes, we conducted a retrospective study to evaluate the incidence and outcome of AHA in 112 CLL patients treated with fludarabine alone. Eight patients had AHA before therapy; only one achieved remission of both CLL and AHA after fludarabine alone. In the other seven patients, we observed no effect or even a worsening of AHA, although the CLL was responding to fludarabine. Five patients developed AHA from 1 to 19 months after fludarabine therapy while the CLL was responding. One additional patient developed pure red cell aplasia (PRCA) 3 months after starting therapy. Most patients in both groups responded to steroids or other immunosuppressive therapy. The study showed that in these patients, AHA evolved independently of CLL and was not affected by fludarabine.
ISSN:1042-8194
DOI:10.3109/10428199309054731
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
|
9. |
Effect of Induction Cytarabine Dose Intensity on Long-Term Survival in Acute Myelogenous Leukemia: Results of a Randomized, Controlled Study |
|
Leukemia&Lymphoma,
Volume 11,
Issue 1-2,
1993,
Page 69-77
SchillerGary,
NimerStephen,
GajewskiJames,
LeeMyung,
HoWinston,
TerritoMary,
ChamplinRichard,
Preview
|
PDF (635KB)
|
|
摘要:
The optimal dose and schedule of cytarabine in induction chemotherapy of newly diagnosed acute myelogenous leukemia is not established. We compared the use of cytarabine 200 mg/ m*/day by continuous infusion for seven days to an intermediate-dose of cytarabine, 500 mg/m- every 12 hours for 12 doses. Thirty-seven of 52 patients assigned to conventional-dose cytarabine achieved complete remission (71%) and the actuarial disease-free and overall survival after achieving remission were 22±16% and 31 t 19% respectively. Thirty-seven of 50 patients assigned to intermediate-dose cytarabine achieved remission (74%) and the actuarial disease-free and overall survival after achieving remission were 26±16% and 39±18% respectively. There were no statistically significant differences in complete remission rate, actuarial leukemia-free survival or overall survival between the groups. The most significant predictor for survival was age. Actuarial two year leukemia-free survival and overall survival for patients age>60 were 8±15% and 20±19% respectively compared to 36 2 14% and 54±15% for patients age≤60 (P =.058 and. 01, respectively). Induction regimen did not significantly affect disease free or overall survival for patients under or over age 60. We conclude that intermediate-dose cytarabine did not substantially improve results of induction for newly diagnosed acute myeloid leukemia.
ISSN:1042-8194
DOI:10.3109/10428199309054732
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
|
10. |
Role of Aberrant Sialylation of Chronic Myeloid Leukemia Granulocytes on Binding and Signal Transduction by Chemotactic Peptides and Colony Stimulating Factors |
|
Leukemia&Lymphoma,
Volume 11,
Issue 1-2,
1993,
Page 79-90
CyopickPaul,
CullitonRaymond,
BrockhausenInka,
SutherlandD. Robert,
MillsGordon B.,
BakerMichael,
Preview
|
PDF (886KB)
|
|
摘要:
Chronic myelogenous leukemia (CML) granulocytes exhibit a number of characteristics attributable to immature granulocytes, including marked increases in cell surface sialylation of glycoproteins which may be due, at least in part, to an increased activity of cytidine 5‘-monophosphate-N-acetylneuraminic acid: Ga1βl -3Gal NAcα(2–3)-sialytransferase (EC 2.4.99.4), and perhaps to altered activity of other glycosyltransferases and sialidases. This aberrant sialylation of CML granulocytes contributes to the decreased binding of the synthetic chemotactic peptide, formyl Met Leu Phe (fMLP), to the surface of CML granulocytes which leads to a rapid, transient increase in cytosolic free calcium ([Ca2+]1), an integral step in the biochemical cascade leading to cell activation. To determine if the decrease in binding of fMLP to CML granulocytes translates into a functional deficit, we measured fMLP-induced increases in [Ca2+]1. Compared to normal granulocytes, fMLP-induced increases in [Ca2+]iwere markedly decreased in CML granulocytes. After sialidase treatment, a significant augmentation in fMLP-induced increases in [Ca2+]iwas noted in CML granulocytes, indicating that the decreased signalling may be a consequence of aberrant sialylation. To determine if the effects of aberrant sialylation also alters the binding of endogenous polypeptide mediators, we determined the effect of desialylation of CML and normal granulocytes on binding of the colony stimulating factor for granulocytes and monocytes (GM-CSF), which plays a role in differentiation and proliferation of myeloid-lineage cells. As with fMLP binding, we also showed that the binding of GM-CSF to CML granulocytes, but not normal granulocytes, was markedly increased after sialidase treatment. Similarly, binding of GM-CSF to undifferen-tiated HL-60 cells was markedly increased after sialidase treatment. Therefore, we have demonstrated that aberrant sialylation of CML granulocytes not only alters the binding of fMLP and GM-CSF to their receptor(s), but may also alter signal transduction. Thus, aberrant gly-cosylation of CML granulocytes may reduce the binding of hematopoietic growth factors, which in turn may be responsible for the immature phenotype of CML granulocytes.
ISSN:1042-8194
DOI:10.3109/10428199309054733
出版商:Taylor&Francis
年代:1993
数据来源: Taylor
|
|