T cells and probably B cells arise from the malignant clone in chronic myelogenous leukemia.

Fauser, AA; Kanz, Lothar; Bross, K. J.; Gw, Löhr

doi:10.1172/jci111771

Cited by 58 publications

(11 citation statements)

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“…This is in keeping with recent evidence supporting the concept that T cells are part of the malignant clone. 11,12 Treatment of the myeloid blast crisis with a combination of donor lymphocytes and IL-2 infusions resulted in the decline in the number of myeloblasts. A recent paper reports the use of donor lymphocyte infusions in relapsed CML, with response in 13 out of 18 patients and an overall survival of 52% at 5 years.…”

Section: Discussionmentioning

confidence: 99%

“…FISH analysis showed the presence of two copies of the bcr-abl fusion gene in 60% of these cells and one copy in 26% (Figure 1c). Conventional cytogenetics demonstrated additional complex abnormalities (50, XY, t(1;3)(p31;q26), +8, t(9;22)(q34;q11), +19 , +21, der(22)t(9;22)(q34;q11) [11]/50, idem, add(14)(q32) [2] / 46, XY [6]). Bone marrow morphology and immunophenotyping did not show any T lymphoblasts or excess myeloblasts, but cytogenetics showed the presence of cells with similar abnormalities in the bone marrow (50, XY, t(1;3)(p31;q26), +8, t(9;22)(q34;q11), +19, +21, der (22)t(9;22)(q34;q11) [2]/50, XY, idem, add(14)(q32) [5]/50, XY, idem, add(2)(q?)…”

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confidence: 99%

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Extramedullary T lymphoblastic transformation of chronic myeloid leukaemia occurring after double allogeneic transplantation

Kell

Booth

Jones

et al. 1998

Bone Marrow Transplant

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Summary:The clinical course of chronic myeloid leukaemia (CML) is characterised by a chronic phase followed by an acute phase or blast crisis. Lymphoid transformation accounts for 20-30% of such events, with the majority of cases being of B cell origin. Extramedullary transformation occurs in approximately 10% of cases. We report a case of T cell lymphoblastic transformation in CML presenting as an extramedullary mass after allogeneic stem cell transplant. This case supports the growing evidence that CML arises in the pluripotent stem cell. Keywords: chronic myeloid leukaemia; T lymphoblastic transformation; interleukin-2; allogeneic bone marrow transplantation; donor lymphocyte infusion Chronic myeloid leukaemia (CML) is a clonal disorder of haemopoiesis characterised by the Philadelphia chromosome (t(9;22)(q34;q11), Ph). 1 The clinical course comprises a chronic phase, usually lasting 3-5 years, followed by an accelerated phase and blast crisis (BC). The majority of blast crises are of myeloid phenotype, and lymphoid transformation occurs in 20-30% of cases. Lymphoblasts expressing CD10 are by far the most common and a T cell phenotype is extremely rare. 2 Most reported cases of T lymphoblastic transformation occurred either in the bone marrow or within the lymphoreticular system. We report a patient with Ph-positive CML in whom treatment of a postallogeneic bone marrow transplant myeloid blast crisis with donor lymphocyte and IL-2 infusions followed by a second transplant was complicated by extramedullary T lymphoblastic tumour development. pable at the umbilicus. His white cell count was elevated at 327 × 10 9 /l and the peripheral blood was consistent with a diagnosis of CML. Conventional cytogenetic analysis confirmed the presence of the t(9;22)(q34;q11) Philadelphia chromosome with no other cytogenetic abnormality. He was initially managed by leucapheresis and hydroxyurea. ␣-Interferon (IFN␣) was added later. He did not have a major cytogenetic response to IFN␣.In October 1996 he underwent an allogeneic bone marrow transplant from an HLA-matched male sibling donor. He received busulphan 4 mg/kg p.o. in divided doses daily for 4 days (total 16 mg/kg) and cyclophosphamide 60 mg/kg once daily i.v. on days 1 and 2 (total 120 mg/kg) as conditioning regimen and cyclosporin A and methotrexate (10 mg/m 2 on days 1, 3 and 6) as graft-versus-host disease (GVHD) prophylaxis. The peri-transplant period was uneventful except for the development of haemorrhagic cystitis. He did not develop any significant acute GVHD. His neutrophil count reached 0.5 × 10 9 /l on day 20 and platelets reached 20 × 10 9 /l on day 10.He developed a bone marrow myeloid blast crisis 3 months following the allogeneic BMT. Immunophenotyping confirmed myeloid blast crisis with CD13 + , CD33 + cells. There were also increased numbers of CD7 + cells. Cytogenetic analysis showed evidence of clonal disease progression with the acquisition by the Ph + cells of an additional chromosomal abnormality of t(1;3)(p31;q26). Cells with a normal karyotype fo...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Extramedullary T lymphoblastic transformation of chronic myeloid leukaemia occurring after double allogeneic transplantation

Kell

Booth

Jones

et al. 1998

Bone Marrow Transplant

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“…Cells were cultured essentially as described (3,10). PBMC were separated from heparinized blood by Ficoll/Hypaque (Pharmacia) centrifugation and washed.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, cultures of bone marrow (BM) and peripheral blood mononuclear cells (PBMC) from non-Hodgkin lymphoma and chronic myelogenous leukemia patients may produce multilineage colonies with lymphoid and myeloid cells (2,3). We have studied hematopoiesis in cells from patients with hairy cell leukemia (HCL), a disease characterized by pancytopenia and, in BM, spleen, and often peripheral blood, by accumulation of incompletely differentiated, preplasmatic B lymphocytes with low proliferation, with typical morphology, and also with the interleukin 2 receptor Tac antigens as well as unexplained monocyte markers (4)(5)(6).…”

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confidence: 99%

Interferons regulate the in vitro differentiation of multilineage lympho-myeloid stem cells in hairy cell leukemia.

Michalevicz¹,

Revel²

1987

Proc. Natl. Acad. Sci. U.S.A.

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In vitro 14-day cultures of peripheral blood mononuclear cells from hairy cell leukemia patients consistently showed the presence of hematopoietic stem cells giving rise to multilineage colonies containing a high proportion of lymphoid cells associated with the myeloid and erythroid progenitors. These stem cells are not the hairy cells but appear to be pluripotent lymphomyeloid primitive stem cells persisting in this leukemia. Interferon ac or .f1 did not inhibit the growth of these colonies, as they did the growth of colonies of normal hematopoietic progenitors, but markedly decreased the ratio of lymphoid to myelomonocytic cells, by increasing the formation of monocytes and other nonlymphoid cell types in these multilineage colonies. Interferon ydid not have the same effects on differentiation.The existence of hematopoietic primitive stem cells giving rise to the lymphoid progeny, as well as to the other blood cell lineages, has been inferred from the genetic study ofleukemia clones in vivo (1), and these rare cells seem to be detectable in a few hematopoietic disorders. Thus, cultures of bone marrow (BM) and peripheral blood mononuclear cells (PBMC) from non-Hodgkin lymphoma and chronic myelogenous leukemia patients may produce multilineage colonies with lymphoid and myeloid cells (2, 3). We have studied hematopoiesis in cells from patients with hairy cell leukemia (HCL), a disease characterized by pancytopenia and, in BM, spleen, and often peripheral blood, by accumulation of incompletely differentiated, preplasmatic B lymphocytes with low proliferation, with typical morphology, and also with the interleukin 2 receptor Tac antigens as well as unexplained monocyte markers (4-6). Long-term interferon (IFN) a injections can reduce the hairy cell mass but, more strikingly, restore the levels of granulocytes, macrophages, platelets, and erythrocytes in HCL patients (7-9).In vitro hematopoietic colony cultures from the peripheral blood of HCL patients consistently had multilineage colonies containing many B lymphocytes associated with the myeloid cells but poor in monocytes. These colony-forming cells are distinct from the hairy cells. Type I human recombinant IFN-a or -,3 profoundly affects the differentiation pattern of the HCL lymphomyeloid stem cell cultures: the formation of myeloid and monocytic elements, as well as the formation of normoblasts and megakaryocytes, is enhanced, whereas the number of lymphoid cells decreases. Type II IFN-y has no such effect. These findings may be related to the mechanism by which type I IFNs induce remission and relieve pancytopenia in HCL patients. HCL provides an experimental model for the study of primitive multilineage lymphomyeloid stem cells growth and differentiation and for the study of the effects of IFN on this process. MATERIALS AND METHODSColony-Forming Cultures for Hematopoietic Progenitors. Cells were cultured essentially as described (3, 10). PBMC were separated from heparinized blood by Ficoll/Hypaque (Pharmacia) centrifugation and washed. Cells that d...

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“…In crease in c-myc RNA in normal fibroblasts and lym phocytes during the transition from the quiescent to the proliferating state induced by growth factor or mi togen stimulation has been reported [1], Deregulated expression of c-myc has been observed in B cell lym phomas, Burkitt's lymphoma and isolates of several tumor types. When cells of the human promyelocytic leukemia line HL 60 are induced to differentiate and cease to proliferate, c-myc expression is greatly re duced [2], Mitogen stimulation of peripheral blood T cells of the T4 phenotype derived from healthy do nors leads to the production and release of lympho kines supporting the growth of a noncommitted pro genitor cell population that form multilineage colon ies (CFU-GEMMT) [3,4], We report here the simul taneous increase of c-myc RNA in these lymphokineproducing cells.…”

Section: Introductionmentioning

confidence: 99%

Expression of c-myc in Stimulated T Lymphocytes of the Helper/Inducer Phenotype Producing Lymphokine(s) Supporting Multilineage Colony Formation

Löhr¹,

Gw²,

Kanz³

et al. 1986

Acta Haematol

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Phytohemagglutinin (PHA) renders human peripheral T lymphocytes competent to replicate their DNA and divide. The stimulation of peripheral T cells of the T4 phenotype by PHA, which appears to be a transcription-dependent event, leads to the production and release of lymphokines supporting proliferation and differentiation of human pluripotent stem cells (CFU-GEMMT). Supernatants of PHA-stimulated lymphocytes of the suppressor/cytotoxic phenotype (T8) failed to demonstrate reasonable activity to support the growth of CFU-GEMMT. Stimulation of T lymphocytes of the T4 but not of the T8 phenotype leads to an increased intracellular level of c-myc mRNA. This would be consistent with the c-myc gene product functioning as an intracellular mediator of the growth and lymphokine production response to PHA. Although the function of the c-myc gene product is not yet clear, it seems likely that it is involved in the control of cell proliferation. Such a contribution to control of cell proliferation by c-myc would probably be mediated by a family of genes inducing lymphokine production to stimulate proliferation of human pluripotent stem cells.

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T cells and probably B cells arise from the malignant clone in chronic myelogenous leukemia.

Cited by 58 publications

References 14 publications

Extramedullary T lymphoblastic transformation of chronic myeloid leukaemia occurring after double allogeneic transplantation

Extramedullary T lymphoblastic transformation of chronic myeloid leukaemia occurring after double allogeneic transplantation

Interferons regulate the in vitro differentiation of multilineage lympho-myeloid stem cells in hairy cell leukemia.

Expression of c-myc in Stimulated T Lymphocytes of the Helper/Inducer Phenotype Producing Lymphokine(s) Supporting Multilineage Colony Formation

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