Case report: T‐cell acute lymphoblastic leukemia relapsing as acute myelomonocytic leukemia and terminating possibly as chronic myelocytic leukemia

Shimizu, Jyoji; Hamashima, Yoshihiro; Tsuda, Hideo; Akiyama, Yuichi; Mikawa, Harukí; Ikehara, Susumu

doi:10.1002/ajh.2830240211

Cited by 5 publications

(1 citation statement)

References 16 publications

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“…And it is now accepted that leukemia and preleukemia are ‘stem cell disorders’ [48]; in 1987, we presented a case report (T-cell acute lymphoblastic leukemia relapsing as acute myelocytic leukemia and terminating possibly as chronic myelocytic leukemia), and proposed that leukemia originates in a P-HSC [49]. Here we would like to propose the concept that ‘stem cell disorders’ include autoimmune diseases.…”

Section: New Concept Of ‘Stem Cell Disorder’mentioning

confidence: 99%

Bone Marrow Transplantation for Autoimmune Diseases

Ikehara¹

1998

Acta Haematol

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Bone marrow transplantation (BMT) is now becoming a powerful strategy for the treatment of patients with autoimmune diseases. Using various animal models for autoimmune diseases, we have previously found that allogeneic BMT (not autologous BMT) can be used to treat autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), immune thrombocytic purpura, insulin-dependent diabetes mellitus (IDDM), chronic glomerulonephritis, and certain types of non-insulin-dependent diabetes mellitus. In contrast, we have found that the transplantation of T-cell-depleted bone marrow cells or partially purified hemopoietic stem cells (HSCs) from autoimmune-prone mice to normal mice leads to the induction of autoimmune diseases in the recipients. These findings have recently been confirmed even in humans; autoimmune diseases such as RA, SLE, multiple sclerosis, and Crohn’s disease were resolved after allogeneic BMT. However, there have recently been reports on the rapid recurrence or persistence of autoimmune diseases after autologous BMT. Conversely, the adoptive transfer of autoimmune diseases such as myasthenia gravis, IDDM and Graves’ disease by allogeneic BMT from donors to recipients has been reported. Based on these findings, we have proposed that autoimmune disease is ‘a stem cell disorder’. To clarify the differences between normal and abnormal HSCs, we have established a new method for purifing HSCs. Using this method, we purified HSCs from normal and autoimmune-prone mice and compared the former with the latter. We have found that a major histocompatibility complex (MHC) restriction exists between normal HSCs and stromal cells, whereas there is no MHC restriction between abnormal HSCs and stromal cells either in vivo or in vitro; abnormal HSCs proliferate even in allogeneic environments. Abnormal HSCs thus appear to be more resilient than normal HSCs. In humans, BMT across MHC barriers has had a low success rate as a consequence of (1) graft-versus-host disease (GVHD), (2) graft rejection and (3) incomplete recovery of T cell functions. However, we have found that such problems can be overcome in mice. GVHD can be prevented if T-cell-depleted bone marrow cells are used. Graft rejection can be prevented by bone grafts to recruit donor stromal cells, since, as we have found, an MHC restriction exists between HSCs and stromal cells. In addition, we have found that stromal cells migrate from the bone marrow to the thymus, where they become engaged in positive selection. Therefore, the bone grafting to recruit donor stromal cells leads to a complete recovery of T cell functions, since T cells, which are positively selected by donor stromal cells in the thymus, can cooperate with donor B cells and antigen-presenting cells. In humans, it is well known that the success rate of BMT in patients more than 45 years old is low. Recently, we have found that the low success rate is due to the aging of the thymus, and that BMT plus embryonal thymus grafts can be used to treat late-onset autoimmune diseases...

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Section: New Concept Of ‘Stem Cell Disorder’mentioning

confidence: 99%

Bone Marrow Transplantation for Autoimmune Diseases

Ikehara¹

1998

Acta Haematol

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Multiple Primary Neoplasms

Kaiser¹

1989

Influence of Tumor Development on the Host

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Secondary Acute Myeloid Leukemia in Children Treated for Acute Lymphoid Leukemia

et al. 1989

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We studied the risk of the development of acute myeloid leukemia (AML) during initial remission in 733 consecutive children with acute lymphoid leukemia (ALL) who were treated with intensive chemotherapy. This complication was identified according to standard morphologic and cytochemical criteria in 13 patients 1.2 to 6 years (median, 3.0) after the diagnosis of ALL. At three years of follow-up, the cumulative risk of secondary AML during the first bone marrow remission was 1.6 percent (95 percent confidence limits, 0.7 and 3.5 percent); at six years, it was 4.7 percent (2 and 10 percent). The development of secondary AML was much more likely among patients with a T-cell than a non-T-cell immunophenotype (cumulative risk, 19.1 percent [6 and 47 percent] at six years). Sequential cytogenetic studies in 10 patients revealed entirely different karyotypes in 9, suggesting the induction of a second neoplasm. In eight of these patients, the blast cells had abnormalities of the 11q23 chromosomal region, which has been associated with malignant transformation of a pluripotential stem cell. There was no evidence of loss of DNA from chromosome 5 or 7, a karyotypic change commonly observed in cases of AML secondary to treatment with alkylating agents, irradiation, or both. We conclude that there is a substantial risk of AML in patients who receive intensive treatment for ALL, especially in those with a T-cell immunophenotype, and that 11q23 chromosomal abnormalities may be important in the pathogenesis of this complication.

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Case report: T‐cell acute lymphoblastic leukemia relapsing as acute myelomonocytic leukemia and terminating possibly as chronic myelocytic leukemia

Cited by 5 publications

References 16 publications

Bone Marrow Transplantation for Autoimmune Diseases

Bone Marrow Transplantation for Autoimmune Diseases

Multiple Primary Neoplasms

Secondary Acute Myeloid Leukemia in Children Treated for Acute Lymphoid Leukemia

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