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Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have retrospectively analyzed the characteristics of 24 adult patients affected with non-endemic Burkitt's lymphoma (BL) and Burkitt cell acute leukemia (L3 ALL). The median age of the entire group was 29 years with a male preponderance (75%). Median LDH value was 580 mU/mL. Test for HIV-antibodies was carried-out in 16 patients; 5 of them (21%) showed HIV positive. CNS was involved in 25% of patients at diagnosis. In all cases studied for karyotype, the t(8;14) translocation was evident. As to therapy, 5 patients were not evaluable for early death, 12 were given an intensive ALL program, 5 a cyclic chemotherapy and 2 a new protocol alternating high-dose cyclophosphamide, high-dose cytarabine with mitoxantrone and the CHOP regimen. The overall complete remission rate was 42%; among 7 remitters, 4 have relapsed so far within a median time of 6 months. Three of 13 (23%) patients with lymphoma presentation are long remitters and may be cured; all cases had stage II disease and low LDH at diagnosis (less than 250 mU/mL). No patients with Burkitt's leukemia survive. CNS disease (8 cases) and septic shock (6 cases) were the most frequent terminal events. In our experience, the prognosis of advanced stage BL and L3 ALL in adults does remain dismal; the high prevalence of CNS disease and HIV-positivity may have contributed to the poor outcome.
Leukemia 1991
PMID:Burkitt's lymphoma/leukemia: a clinicopathologic study on 24 adult patients. 189 Aug 73

Sixty precursor B-cell acute lymphoblastic leukemia (ALL) patients were analyzed for the configuration of their immunoglobulin (Ig) genes. Rearrangements and/or deletions of the Ig heavy chain (IgH), Ig kappa chain (Ig kappa), and Ig lambda chain (Ig lambda) genes were detected in 98, 48, and 23% of cases, respectively. Although these percentages suggest the presence of a hierarchical order in IgH and Ig light chain (IgL) gene rearrangements during B-cell differentiation, no correlation was found between the immunophenotype of the precursor B-ALL and the arrangement patterns of their IgH and IgL genes. Multiple rearranged IgH gene bands, generally differing in density, were found in 27 (45%) of the precursor B-ALL in various restriction enzyme digests. Cytogenetic data were used to determine whether the presence of more than two rearranged IgH gene bands was caused by hyperdiploidy of chromosome 14 or other chromosome 14 aberrations. The combined cytogenetic and IgH gene data allowed the precursor B-ALL to be divided into three groups: a monoclonal group (n = 36; 60%), a biclonal group (n = 16; 27%), and an oligoclonal group (n = 8; 13%). In five biclonal ALL biclonality at the Ig kappa gene level was also found. Such subclone formation was not detected at the Ig lambda gene level. As the detection limit of the Southern blot technique is 2-5%, it might well be that small subclones remained undetected, implying that the frequency of subclone formation at the IgH gene level in precursor B-ALL is probably higher than 40%. It has been suggested that precursor B-ALL with multiple IgH gene rearrangements have a higher tendency to relapse. Although higher relapse rates were found in the oligoclonal group (53%) and in the combined bi-oligoclonal group (33%) compared with the monoclonal group (20%), the log rank trend test showed no significance. The occurrence of multiple subclones in precursor B-ALL as found by IgH gene analyses will severely hamper the detection of minimal residual disease using the polymerase chain reaction (PCR) mediated amplification of 'tumor-specific' IgH gene junctional regions, because it cannot be predicted which detectable (or undetectable) subclone will cause minimal residual disease and/or relapse. Therefore it can be expected that the PCR technique will frequently produce false negative results during the follow-up of precursor B-ALL.
Leukemia 1991 Aug
PMID:Multiple rearranged immunoglobulin genes in childhood acute lymphoblastic leukemia of precursor B-cell origin. 190 9

A cell line, designated HAL-01, was established from the blood cells of a patient with acute lymphoblastic leukemia (ALL) with a myeloid-associated marker. Both the cell line and the patient's fresh leukemia cells had the chromosomal translocation t(17;19)(q21;p13). Morphologically and cytochemically, the cells were lymphoid in appearance. Immunophenotyping of the donor's leukemia cells revealed that they express B lineage antigens (CD10+, CD19+, CD20+, CD22+); the myeloid-associated antigen (CD13) detected in the donor's leukemia cells was not expressed by the established cell line. The HAL-01 cells have a rearrangement of the immunoglobulin heavy chain gene, while the T-cell receptor beta-chain genes remain in the germline configuration. The gene encoding the binding proteins for the kappa-light chain enhancer (kappa E2), which is involved in pre-B-ALL cells with the t(1;19) (q23;p13) translocation, is not rearranged in the cell line. The HAL-01 cells were transplantable into the peritoneum of untreated nude mice where they grew as an ascites tumor. The growing tumor cells also infiltrated lymph nodes, liver, spleen, kidney, and bone marrow without exhibiting a particular change in the morphology of the neoplastic cells. Clonogenic assay in methylcellulose culture demonstrated that the proliferation of the HAL-01 cells was suppressed by interleukin-3 (IL-3) in a dose-dependent fashion, with maximum inhibition occurring at concentrations greater than 100 U/ml. Treatment with IL-3 reduced the number of viable cells as well as induced morphological changes without concomitant changes in cytochemical reactions or immunophenotypic expression. Reduction of 3H-thymidine incorporation by exposure of IL-3 was blocked by the pretreatment of neutralizing anti-IL-3 antibody, but not by neutralizing anti-TGF-beta antibody. Thus, HAL-01 is a unique ALL cell line exhibiting proliferative suppression by IL-3 that may prove useful in studying the interactions of cytokines in ALL.
Leukemia 1991 Apr
PMID:Establishment of a novel heterotransplantable acute lymphoblastic leukemia cell line with a t(17;19) chromosomal translocation the growth of which is inhibited by interleukin-3. 202 99

The aim of this study was to analyze the homing and progression patterns of childhood acute lymphoblastic leukemias (ALL) in mice with severe combined immunodeficiency (SCID). Upon intraperitoneal (IP) transfer, cells from relapse samples of three children with T-lineage ALL spread hematogenously and infiltrated the non-lymphoid and/or lymphoid organs with a pattern reminiscent of the human clinical disease. These mice either died or were killed in extremis at a mean of 9 weeks. Moreover, cell lines established in vitro from two of these samples manifested identical homing and progression in the SCID mouse as compared with the original patients' cells. Thus, long-term culture of the primary leukemic T cells did not alter their invasive potential and migration pattern. When engrafted IP, three cell lines established from pre-B-ALL cases displayed primarily a lymphatic spread with induction of local tumor masses and kidney/liver nodules. Mice were killed at 11 to 13 weeks, but had not developed imminently fatal leukemia. However, when transferred intravenously, one pre-B ALL cell line was able to spread hematogenously and to infiltrate both lymphoid and non-lymphoid tissues. Overall, these data demonstrate that the SCID mouse provides an efficient and reproducible model to study the pathogenesis of childhood ALL, and may be a suitable system for evaluating therapy.
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PMID:Homing and progression patterns of childhood acute lymphoblastic leukemias in severe combined immunodeficiency mice. 203 29

Lymphocyte adhesion to high endothelial venules, a central step during extravasation into lymphoid tissues, involves an 85 to 95-kD class of lymphocyte surface glycoproteins, which fall in the cluster of CD44 antigens. In this paper we describe the expression of this homing receptor glycoprotein during lymphoid development. CD44 expression was examined on a large panel of non-Hodgkin's lymphomas (n = 234) and lymphoid leukemias (n = 44). These tumors, which are the malignant counterparts of normal lymphoid cells "frozen" at a certain stage of maturation/activation, are thought to represent a complete spectrum of lymphoid development from stem cell to mature, activated T and B lymphocyte. It was found that CD44 exhibits a trimodal distribution on developing lymphocytes of both the T and B lineage: the CD44 antigen is expressed at relatively high levels during early stages of lymphoid differentiation, i.e., on prothymocytes and immature precursor B cells (null acute lymphoblastic leukemia (ALL) and common ALL). Subsequently, at the stage of the immature/common thymocyte, the pre-B cell and early B cell (pre-B-ALL and B-ALL), the CD44 antigen is temporarily lost from the cell surface to be reacquired during further T and B cell maturation. At the activated (germinal center) B cell stage. CD44 is heterogeneously expressed. This distribution pattern of the CD44 molecule closely matches the recirculatory versus sessile nature of lymphoid cells at consecutive phases of their development, and thus apparently reflects its homing receptor function. In addition, the relatively high expression of the CD44 antigen in the earliest phases of T and B cell development suggests that the molecule may also be involved in the migration of bone marrow derived lymphoid precursors to their site of maturation.
Leukemia 1990 May
PMID:Expression of a human homing receptor (CD44) in lymphoid malignancies and related stages of lymphoid development. 220 31

In the therapy studies ALL-BFM 83 and 86, immunophenotyping of ALL by monoclonal antibodies was performed in a total of 1162 protocol patients (ALL-BFM 83 n = 578; ALL-BFM 86 n = 584). Both studies yielded similar results with respect to the incidence of immunological subtypes: CD10-negative pre-pre-B ALL (ALL-BFM 83: 3.6%; ALL-BFM 86: 5.3%), common ALL (80.1%; 77.9%), B-ALL (1.9%; 2.8%), pre-T/T-ALL (13.9%; 13.5%). Leukemic cells of 3 patients in the ALL-BFM 83 study lacked lymphoid and myeloid antigens (acute unclassifiable leukemia, 0.5%), and 3 patients in the ALL-BFM 86 study exhibited different blast populations with expression of either myeloid or lymphoid features (acute mixed-lineage leukemia, 0.5%). Coexpression of myeloid antigens (CD13 and/or CD33 and/or CDw65) on lymphoblasts (My-positive ALL) was identified in 35 of the 570 (6.1%) protocol patients prospectively analyzed in the ALL-BFM 86 study. The following associations were observed between the immunological subtype and the clinical risk factors: median age (years)-pre-pre-B 3.0, common 4.3, B- 7.9, pre-T/T-ALL 8.5 (pre-pre-B, common vs. pre-T/T-ALL p = 0.05); median leukocyte counts (x 10(9)/l)-pre-pre-B 80, common 9.1, B- 12.3, pre-T/T-ALL 68.1 (common, B- vs. pre-pre-B, pre-T/T-ALL p less than 0.05). The prognostic relevance of the immunophenotype was evaluated on the basis of the therapeutic results obtained in the ALL-BFM 83 study. A significant difference in the remission rate was only recognizable between patients with common ALL (99.1%) and those with pre-T/T-ALL (93.7%, p less than 0.001). After a median follow-up of 54 months, the probability of event-free survival is 71% for pre-pre-B ALL, 67% for common ALL, 56% for pre-T/T-ALL and 27% for B-ALL (common vs. B-, pre-T/T-ALL p less than 0.001), the prognosis in patients with pre-pre-B and common ALL being markedly influenced by the initial leukocyte counts and the age.
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PMID:[Incidence, clinical markers and prognostic significance of immunologic subtypes of acute lymphoblastic leukemia (ALL) in children: experiences of the ALL-BFM 83 and 86 studies]. 220 38

The thermal sensitivities of four B-cell precursor acute lymphoblastic (ALL) cell lines (REH and KM-3 = pre pre B-ALL; NALM-6 and HPB-NULL = pre B-ALL), and 1 B-cell ALL (NAMALWA) cell line were studied and compared to the thermal sensitivity of the T-lineage ALL cell line MOLT-3 using an in vitro clonogenic assay system by limiting dilution. B-lineage ALL cells were as sensitive to hyperthermia as were T-lineage ALL cells. D0 values at 42 degrees C ranged from 44.9 min (NALM-6) to 85.6 min (NAMALWA), D0 values at 43 degrees C ranged from 15.3 min (NALM-6) to 35.7 min (KM-3), and D0 values at 44 degrees C ranged from 11.1 min (NALM-6) to 23.8 min (HPB-NULL). By comparison, the D0 values of MOLT-3 cells were 95.1 min at 42 degrees C, 23.8 min at 43 degrees C, and 14.7 min at 44 degrees C. The maximum log kill values which were observed ranged from 0.8 log (KM-3 and HPB-NULL) to 1.3 logs (NALM-6) at 42 degrees C, from 1.4 logs (KM-3) to 4.2 logs (NALM-6) at 43 degrees C, and from 3.8 logs (HPB-NULL) to 4.8 logs (NALM-6) at 44 degrees C. A thermal tolerant plateau was observed in the hyperthermia survival curves of REH, NALM-6, and HPB-NULL cells, providing circumstantial evidence that thermal tolerance may develop in some B-cell precursor ALL cells after 90-120 min of continuous heating. In contrast, no thermal tolerant plateau was observed in the hyperthermia survival curves of pre-pre-B-ALL/KM-3 B-cell ALL/NAMALWA or T-lineage ALL/MOLT-3 cells. The kinetics of development and decay of thermotolerance was studied for NALM-6 cells. Thermotolerance after a priming heat exposure to 42 degrees C for 30 min was maximum at 8 hr with a maximum thermotolerance ratio of 2.0, and it decayed by 24 hr. These findings extend previous studies on the thermal sensitivity of human leukemia cells and provide new information on the thermal sensitivity and thermotolerance of B-lineage ALL cells.
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PMID:Thermal sensitivity and thermal tolerance of human B-lineage acute lymphoblastic leukemia (ALL) cells. 229 18

In earlier studies of the cytogenetic characteristics of leukemic lymphoblasts from children with pre-B-cell acute lymphoblastic leukemia (ALL), we concluded that certain chromosomal abnormalities explain, in part, the increased presence of high-risk features at diagnosis and the less favorable response to therapy among patients with this immunologic subclass of ALL. With extended follow-up and a larger patient population, we have further evaluated the biologic and clinical aspects of pre-B leukemia. Of 686 cases of ALL with adequate immunophenotyping, 150 were classified as pre-B cell. Seventy-seven (69%) of the 112 pre-B cases with fully banded karyotypes had a translocation. The t(1;19) accounted for 28 (25%) of these pre-B cases and 31 (6.5%) of all 480 consecutively banded ALL cases. Three (2.6%) of the pre-B cases had a novel dicentric (7;9)(p1?3;p11) translocation. A t(9;22)(q34;q11) and a t(4;11)(q21;q23) were observed in seven (6%) and three (2.6%) of the cases, respectively. Within the pre-B subgroup, comparison of t(1;19) cases (n = 28) with those having other translocations (n = 49) or no identifiable translocations (n = 35) indicated that higher leukocyte counts (P = .002), absence of DNA indexes greater than 1.16 (P = .02), higher serum lactate dehydrogenase levels (P less than .0001), and a higher frequency of nonwhite race (P = .006) were significantly related to the t(1;19). Both the t(1;19) and other chromosomal translocations were associated with an adverse prognosis in the subset of patients treated from 1979 to 1984 (Total Therapy study X). In a more recent and more intensive chemotherapy program (Total Therapy study XI), neither the t(1;19) nor other chromosomal translocations has conferred an inferior outcome, suggesting that effective treatment can offset the negative impact of chromosomal rearrangements in cases of childhood pre-B ALL.
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PMID:Cytogenetics of pre-B-cell acute lymphoblastic leukemia with emphasis on prognostic implications of the t(1;19). 238 Jul 59

We investigated the effects of interleukin-7 (IL-7), a stromal cell derived cytokine known to stimulate proliferation of murine lymphoid precursor cells, alone and in combination with IL-3, IL-1, and IL-6 on proliferation of purified blast cells in acute lymphoblastic leukemia (ALL). After 7 days of liquid culture DNA-synthesis was induced in six of 10 cALL, three of five B-ALL, and two of seven T-ALL samples by IL-7 or IL-3 or both. Monitoring of leukemic cell populations in suspension culture by Southern blot analysis of immunoglobulin and T cell receptor gene rearrangements revealed preferential stimulation of the leukemic cell clone by both IL-7 or IL-3 in one cALL and one B-ALL sample. In these cases the combination of IL-7, IL-3, and IL-1 was as effective in stimulation of DNA-synthesis as the most potent cytokine alone. There was no evidence of lymphoid maturation during liquid culture as defined by immunophenotyping using flow cytometry. Stimulation of nonleukemic cell population seen in two other cases of cALL was associated with residual erythroid and granulocyte-macrophage colony forming cells after liquid culture as defined in parallel clonogenic assays in one and detection of CD 33+ and CD 13+ cells after culture in the other cALL sample. We conclude that IL-7 directly stimulates monoclonal growth of leukemic cells in a subset of ALL without evidence of concurrent maturation induction.
Leukemia 1990 Aug
PMID:Effects of recombinant human IL-7 on blast cell proliferation in acute lymphoblastic leukemia. 238 82

Thirty-two children or adolescents had B cell acute lymphocytic leukemia (ALL) diagnosed by demonstration of surface immunoglobulin expression on greater than 10% of their bone marrow blasts. All patients had greater than 25% bone marrow lymphoblasts. Only five of 32 patients (16%) presented with an abdominal mass; however, 24 cases (75%) had FAB L3 morphology. By comparison with findings in common ALL, these 32 children were older (median age, 8 years) and had a higher incidence of central nervous system disease at presentation (22%); all but one were white, and 24 were males. Blast cells from individual cases expressed mu kappa (n = 13), mu lambda (n = 9), gamma kappa (n = 1), alpha kappa (n = 1), or mu with an undetermined light chain (n = 8). The most frequently identified cytogenetic abnormality was the classic B cell-associated t(8;14)(q23;q24) (n = 4); the t(1;19)(q23;p13.3), t(9;22)(q23;q11), and t(1;22) were observed in single cases. Twenty patients were treated uniformly on a single protocol designed for children with advanced B cell malignancy; therapy for the other 12 children varied. Nine children (28%) are surviving event-free; all but one for 3 years or more. We conclude that approximately 25% of children with B cell ALL are curable with intensive multiagent chemotherapy and that classification by immunophenotyping is superior to use of clinical and/or lymphoblast morphologic features.
Leukemia 1990 Jan
PMID:Clinical and biological heterogeneity of childhood B cell acute lymphocytic leukemia: implications for clinical trials. 240 63


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