Bone marrow T helper cells with a Th1 phenotype induce activation and proliferation of leukemic cells in precursor B acute lymphoblastic leukemia patients

Abstract An assay system in vitro for the growth of malignant lymphoblastic colony-forming cells (CFC) was established. Growth of malignant myeloblastic CFC has been previously reported, but this is the first report of growth of malignant lymphoblastic CFC. Established assay systems in vitro have been very helpful in elucidating the control of growth and differentiation of both normal and malignant bone marrow cells. Lymphoblastic CFC were grown from the bone marrow aspirates of 20 children with acute lymphoblastic leukemia. Growth of these colonies was established on an agar assay system and maintained in the relative hypoxia (7% oxygen) of a Stulberg chamber. The criteria for malignancy of these colonies was based upon cellular cytochemical staining characteristics, the presence of specific cell surface markers, and the ability of these lymphoid cells to grow without the addition of a lymphoid mitogen. With this technique, specific nutritional requirements and drug sensitivities can be established in vitro, and these data may permit tailoring of individual antileukemic therapy.

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Low molecular weight B-cell growth factor and recombinant interleukin-2 are together able to generate cytotoxic T lymphocytes with LAK activity from the bone marrow cells of children with acute lymphoblastic leukemia

Blood ◽

10.1182/blood.v74.4.1355.1355 ◽

1989 ◽

Vol 74 (4) ◽

pp. 1355-1359 ◽

Cited By ~ 1

Author(s):

MX Zhou ◽

HW Jr Findley ◽

AH Ragab

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Growth Factor ◽

Cytotoxic T Lymphocytes ◽

Lymphoblastic Leukemia ◽

Interleukin 2 ◽

Leukemic Cells ◽

Recombinant Interleukin 2 ◽

B Cell Growth Factor ◽

Lak Activity

Abstract We are reporting here that low-mol wt B-cell growth factor (LMW-BCGF) and recombinant interleukin-2 (rIL-2) are together able to induce CD3+ cytotoxic T lymphocytes (CTL) with lymphokine-activated killer cell (LAK) activity from the bone marrow (BM) cells of children with acute lymphoblastic leukemia (ALL). Ficoll-Hypaque (FH)-separated BM cells were obtained from patients with active disease (at diagnosis N = 13, in relapse N = 15) and in complete remission (CR; N = 12). CD3+ cells were removed by Leu-4 antibody and immunobeads. Cells were cultured (10(5) cells/mL) in semisolid media with rIL-2 (100 mu/mL), LMW-BCGF (0.1 mu/mL), and the combination of rIL-2 plus LMW-BCGF, respectively, for seven to ten days. Pooled colonies were harvested for phenotyping. LMW-BCGF plus rIL-2 induced large numbers of CD3+ colonies from CD3- precursors. rIL-2 alone did not induce colony formation. In addition, cells were cultured in liquid media with LMW-BCGF, rIL-2, and the combination of LMW-BCGF plus rIL-2, respectively, for seven to 21 days. They were harvested for phenotyping, and cytotoxicity assays were performed v K562, Raji, and autologous leukemic cells. LMW-BCGF plus rIL-2 induced significant expansion of CD3+ cells from CD3- precursors, and these cells were activated to kill autologous leukemic cells in addition to Raji and K562 cell lines. LMW-BCGF or rIL-2 alone did not induce significant expansion or activation of cytotoxic CD3- cells. Our hypothesis is that LMW-BCGF plus rIL-2 stimulates the proliferation and activation of CD3- precursors from the BM cells of children with acute leukemia to become CD3+ cells that have LAK activity. This finding may have therapeutic implications.

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Monocytes are activated in patients with myelodysplastic syndromes and can contribute to bone marrow failure through CD40–CD40L interactions with T helper cells

Leukemia ◽

10.1038/sj.leu.2404940 ◽

2007 ◽

Vol 21 (12) ◽

pp. 2411-2419 ◽

Cited By ~ 14

Author(s):

S Meers ◽

A Kasran ◽

L Boon ◽

J Lemmens ◽

C Ravoet ◽

...

Keyword(s):

Bone Marrow ◽

Myelodysplastic Syndromes ◽

T Helper Cells ◽

Bone Marrow Failure ◽

T Helper ◽

Helper Cells

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Bone marrow from children in relapse with pre-B acute lymphoblastic leukemia proliferates and disseminates rapidly in scid mice

Blood ◽

10.1182/blood.v78.11.2973.bloodjournal78112973 ◽

1991 ◽

Vol 78 (11) ◽

pp. 2973-2981 ◽

Cited By ~ 2

Author(s):

S Kamel-Reid ◽

M Letarte ◽

M Doedens ◽

A Greaves ◽

B Murdoch ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Poor Prognosis ◽

Lymphoblastic Leukemia ◽

Growth Characteristics ◽

Scid Mice ◽

Leukemic Cells ◽

Murine Bone Marrow ◽

In Vivo Growth

Bone marrow samples from patients with pre-B acute lymphoblastic leukemia (pre-B ALL), either at diagnosis or at relapse, were transplanted into scid mice to determine whether these freshly obtained leukemic cells could proliferate in vivo and whether there were any differences in their in vivo growth characteristics. Cells from three patients who relapsed within 13 months of diagnosis proliferated rapidly in the murine bone marrow, spleen, and thymus, invaded peripheral organs, and resulted in morbidity and mortality of the animals within 4 to 16 weeks. Cells from two patients who relapsed 3.5 years after diagnosis grew much slower than the early relapse samples, taking up to 30 weeks to infiltrate the bone marrow of recipient mice. In contrast, leukemic cells were absent or were detected at low numbers in scid mice transplanted with cells obtained at diagnosis from three patients who have not yet relapsed. These results show an increased ability of leukemic cells from patients with aggressive lymphoblastic leukemia of poor prognosis to proliferate in scid mice.

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Serotherapy of acute lymphoblastic leukemia with monoclonal antibody

Blood ◽

10.1182/blood.v58.1.141.141 ◽

1981 ◽

Vol 58 (1) ◽

pp. 141-152 ◽

Cited By ~ 201

Author(s):

J Ritz ◽

JM Pesando ◽

SE Sallan ◽

LA Clavell ◽

J Notis-McConarty ◽

...

Keyword(s):

Monoclonal Antibody ◽

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Chemotherapeutic Agents ◽

Leukemic Cells ◽

Antigenic Modulation ◽

Multiple Intravenous Infusions ◽

Marrow Cellularity

Abstract We tested the efficacy of passive serotherapy in the treatment of acute lymphoblastic leukemia in four patients who had relapsed while receiving standard chemotherapeutic agents. Each patient received multiple intravenous infusions of J-5 monoclonal antibody specific for common acute lymphoblastic leukemia antigen (CALLA). In the three patients with circulating leukemic cells, there was a rapid decrease in circulating blasts that began immediately after antibody infusion, but not all leukemic cells were cleared, and remaining cells appeared to be resistant to further serotherapy. Although J-5 antibody was also demonstrable on bone marrow lymphoblasts immediately after antibody infusion in one patient, there was no change in bone marrow cellularity or differential during serotherapy. Analysis of the cell surface phenotype of leukemic cells during serotherapy and in vitro studies with patient cells suggests that resistance to serotherapy was mediated in part by antigenic modulation of CALLA in response to J-5 antibody.

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CD2 antigen expression on leukemic cells as a predictor of event-free survival after chemotherapy for T-lineage acute lymphoblastic leukemia: a Children's Cancer Group study

Blood ◽

10.1182/blood.v88.11.4288.4288 ◽

1996 ◽

Vol 88 (11) ◽

pp. 4288-4295 ◽

Cited By ~ 3

Author(s):

FM Uckun ◽

PG Steinherz ◽

H Sather ◽

M Trigg ◽

D Arthur ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

High Risk ◽

Lymphoblastic Leukemia ◽

Antigen Expression ◽

Leukemic Cells ◽

Event Free Survival ◽

Free Survival ◽

Cancer Group ◽

Standard Risk

Abstract We examined the prognostic impact of CD2 antigen expression for 651 patients with T-lineage acute lymphoblastic leukemia (ALL), who were enrolled in front-line Childrens Cancer Group treatment studies between 1983 and 1994. There was a statistically significant correlation between the CD2 antigen positive leukemic cell content of bone marrow and probability of remaining in bone marrow remission, as well as overall event-free survival (EFS) (P = .0003 and P = .002, log-rank tests for linear trend). When compared with patients with the highest CD2 expression level (> 75% positivity), the life table relative event rate (RER) was 1.22 for patients with intermediate range CD2 expression level (30% to 75% positivity) and 1.81 for “CD2-negative” patients (< 30% positivity). At 6 years postdiagnosis, the EFS estimates for the three CD2 expression groups (low positivity to high positivity) were 52.8%, 65.5%, and 71.9%, respectively. CD2 expression remained a significant predictor of EFS after adjustment for the effects of other covariates by multivariate regression, with a RER of 1.47 for CD2- negative patients (P = .04). Analysis of T-lineage ALL patients shows a significant separation in EFS after adjustment for the National Cancer Institute (NCI) age and white blood cell (WBC) criteria for standard and high-risk ALL (P = .002, RER = 1.67). The determination of CD2 expression on leukemic cells helped identify patients with the better and poorer prognoses in both of these risk group subsets. For standard risk T-lineage ALL, CD2-negative patients had a worse outcome (P = .0007, RER = 2.92) with an estimated 5-year EFS of 55.9% as compared with 78.3% for the CD2-positive patients. Thus, CD2 negativity in standard risk T-lineage ALL identified a group of patients who had a worse outcome than high-risk T-lineage ALL patients who were CD2 positive. The percentage of CD2 antigen positive leukemic cells from T- lineage ALL patients is a powerful predictor of EFS after chemotherapy. This prognostic relationship is the first instance in which a biological marker in T-lineage ALL has been unequivocally linked to treatment outcome.

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Acute Lymphoblastic Leukemia with Mature Appearing Lymphocytes: First Chinese Case Report and Literature Review

Blood ◽

10.1182/blood.v112.11.4896.4896 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4896-4896

Author(s):

QiGuo Zhang ◽

Jian Ouyang ◽

Jianyong Li

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Poor Response ◽

Chromosome 8 ◽

Leukemic Cells ◽

Fish Analysis ◽

Ki 67 ◽

Diffuse Infiltration ◽

Response To Chemotherapy

Abstract Objective: To increase the knowledge and understanding of acute lymphoblastic leukemia with maturation(ALLm). Method: One ALLm case with clinical manifestation, bone marrow morphology, immunophenotype and cytogenetic results were presented and related literatures were reviewed. Result: The patient was a fifty-five year old women, the haematological feature was Pancytopenia. There were 12% lymphoblasts and 82.5% mature appearing lymphocytes in the bone marrow smear. The mature appearing leukemic cells could not be separated clearly by gating. However, the immunophenotypes of mature-appearing leukemic cells(Low FSC and Low CD45) and lymphoblasts were the same. Both results were CD33+CD34+CD19+CD22+HLA−DR+CD5−CD7−CD10−CD13−CD14−CD15−CD20−CD25−CD45−CD71−CD11b−CD103−CD117−. Bone marrow biopsy showed hypercellularity with diffuse infiltration of lymphocytes, The results were CD34++,TdT++,Pax-5+++,CD43++,CD3+(scatter),CD5+(scatter),CD20−,CD10+,CyclinD1−, lymphoblasts Ki67+, mature-appearing leukemic cells ki-67-. FISH analysis of the bone marrow revealed about 1% cells with a signal pattern suggesting loss of one copy of chromosome 8. After VDP, MA, AAG and HAG regimens Complete remission was not achieved. Conclusion: ALLm is a special morphological variant of acute lymphoblastic leukemia, most mature appearing cells are in resting G0 phase and this could be the reason why ALLm has a poor response to chemotherapy.

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Colony formation in vitro by leukemic cells in acute lymphoblastic leukemia (ALL)

Blood ◽

10.1182/blood.v52.4.712.bloodjournal524712 ◽

1978 ◽

Vol 52 (4) ◽

pp. 712-718 ◽

Cited By ~ 1

Author(s):

SD Smith ◽

EM Uyeki ◽

JT Lowman

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Bone Marrow Cells ◽

Lymphoblastic Leukemia ◽

Lymphoid Cells ◽

Assay System ◽

Leukemic Cells ◽

Specific Cell ◽

Specific Cell Surface

An assay system in vitro for the growth of malignant lymphoblastic colony-forming cells (CFC) was established. Growth of malignant myeloblastic CFC has been previously reported, but this is the first report of growth of malignant lymphoblastic CFC. Established assay systems in vitro have been very helpful in elucidating the control of growth and differentiation of both normal and malignant bone marrow cells. Lymphoblastic CFC were grown from the bone marrow aspirates of 20 children with acute lymphoblastic leukemia. Growth of these colonies was established on an agar assay system and maintained in the relative hypoxia (7% oxygen) of a Stulberg chamber. The criteria for malignancy of these colonies was based upon cellular cytochemical staining characteristics, the presence of specific cell surface markers, and the ability of these lymphoid cells to grow without the addition of a lymphoid mitogen. With this technique, specific nutritional requirements and drug sensitivities can be established in vitro, and these data may permit tailoring of individual antileukemic therapy.

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Different Kinetic Pattern of Chronic Myeloid Leukemia: Lymphoblastic and Myeloblastic Blastic Crisis

Tumori Journal ◽

10.1177/030089168006600303 ◽

1980 ◽

Vol 66 (3) ◽

pp. 295-303

Author(s):

Wanda Piacibello ◽

Massimo Aglietta ◽

Felice Gavosto

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Lymphoblastic Leukemia ◽

Kinetic Studies ◽

Leukemic Cells ◽

Cell Kinetic ◽

Blastic Crisis ◽

Kinetic Pattern

Cell kinetic studies were performed in 8 ease of lymphoid blastic crisis (BC) of chronic myeloid leukemia at the onset of BC and during subsequent relapses. The results were compared with those found in 7 myeloblastic BC. While in the myeloblastic transformation the labeling index (LI) was always higher in bone marrow than in peripheral blood blasts, suggesting a predominant bone marrow proliferation of the leukemic cells, in the lymphoid transformation a higher LI was often found in peripheral blasts. Moreover, the lymphoblastic transformations were frequently characterized by lymphadenopathy. These findings point to the similarities between lymphoid BC and acute lymphoblastic leukemia, suggesting the possibility that a blastic event may originate in an extramedullary site and that an extramedullary BC is more likely to be lymphoid in nature.

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