Acute lymphoblastic leukemia arising after treatment of Ewing sarcoma was misdiagnosed as bone marrow metastasis of Ewing sarcoma

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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Heterozygous PALB2 Mutation in a Boy with Acute Lymphoblastic Leukemia and Subsequent Metastatic Ewing Sarcoma

Klinische Pädiatrie ◽

10.1055/a-1404-3243 ◽

2021 ◽

Author(s):

Carla Mehaffey ◽

Dagmar Wahl ◽

Tina Schaller ◽

Mirjam Blattner-Johnson ◽

Rainer Claus ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Ewing Sarcoma ◽

Lymphoblastic Leukemia ◽

Palb2 Mutation

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Co-culture model of B-cell acute lymphoblastic leukemia recapitulates a transcription signature of chemotherapy-refractory minimal residual disease

Scientific Reports ◽

10.1038/s41598-021-95039-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Stephanie L. Rellick ◽

Gangqing Hu ◽

Debra Piktel ◽

Karen H. Martin ◽

Werner J. Geldenhuys ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

B Cell ◽

Tumor Cells ◽

Minimal Residual Disease ◽

Residual Disease ◽

Lymphoblastic Leukemia ◽

Adherent Cells ◽

Cell Acute Lymphoblastic Leukemia ◽

Minimal Residual

AbstractB-cell acute lymphoblastic leukemia (ALL) is characterized by accumulation of immature hematopoietic cells in the bone marrow, a well-established sanctuary site for leukemic cell survival during treatment. While standard of care treatment results in remission in most patients, a small population of patients will relapse, due to the presence of minimal residual disease (MRD) consisting of dormant, chemotherapy-resistant tumor cells. To interrogate this clinically relevant population of treatment refractory cells, we developed an in vitro cell model in which human ALL cells are grown in co-culture with human derived bone marrow stromal cells or osteoblasts. Within this co-culture, tumor cells are found in suspension, lightly attached to the top of the adherent cells, or buried under the adherent cells in a population that is phase dim (PD) by light microscopy. PD cells are dormant and chemotherapy-resistant, consistent with the population of cells that underlies MRD. In the current study, we characterized the transcriptional signature of PD cells by RNA-Seq, and these data were compared to a published expression data set derived from human MRD B-cell ALL patients. Our comparative analyses revealed that the PD cell population is markedly similar to the MRD expression patterns from the primary cells isolated from patients. We further identified genes and key signaling pathways that are common between the PD tumor cells from co-culture and patient derived MRD cells as potential therapeutic targets for future studies.

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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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Pubertal development and final height after autologous bone marrow transplantation for acute lymphoblastic leukemia

Bone Marrow Transplantation ◽

10.1038/sj.bmt.1704324 ◽

2003 ◽

Vol 33 (2) ◽

pp. 205-210 ◽

Cited By ~ 34

Author(s):

P Frisk ◽

J Arvidson ◽

J Gustafsson ◽

G Lönnerholm

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Lymphoblastic Leukemia ◽

Final Height ◽

Pubertal Development ◽

Autologous Bone Marrow Transplantation ◽

Autologous Bone Marrow ◽

Autologous Bone

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Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group

Blood ◽

10.1182/blood-2007-09-114082 ◽

2008 ◽

Vol 111 (6) ◽

pp. 2984-2990 ◽

Cited By ~ 33

Author(s):

Stella M. Davies ◽

Michael J. Borowitz ◽

Gary L. Rosner ◽

Kristin Ritz ◽

Meenakshi Devidas ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Minimal Residual Disease ◽

Residual Disease ◽

Lymphoblastic Leukemia ◽

Response To Therapy ◽

Oncology Group ◽

Risk Status ◽

Prognostic Features ◽

Minimal Residual

Abstract Minimal residual disease (MRD) as a marker of antileukemic drug efficacy is being used to assess risk status and, in some cases, to adjust the intensity of therapy. Within known prognostic categories, the determinants of MRD are not known. We measured MRD by flow cytometry at day 8 (in blood) and at day 28 (in bone marrow) of induction therapy in more than 1000 children enrolled in Pediatric Oncology Group therapy protocols 9904, 9905, and 9906. We classified patients as “best risk” if they had cleared MRD by day 8 of therapy and as “worst risk” if they had MRD remaining in bone marrow at day 28, and tested whether MRD was related to polymorphisms in 16 loci in genes hypothesized to influence response to therapy in acute lymphoblastic leukemia (ALL). After adjusting for known prognostic features such as presence of the TEL-AML1 rearrangement, National Cancer Institute (NCI) risk status, ploidy, and race, the G allele of a common polymorphism in chemokine receptor 5 (CCR5) was associated with more favorable MRD status than the A allele (P = .009, logistic regression), when comparing “best” and “worst” risk groups. These data are consistent with growing evidence that both acquired and host genetics influence response to cancer therapy.

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