Diamond Blackfan anaemia: differential pattern of <i>in vitro</i> progenitor response to macrophage inflammatory protein 1‐alpha

McGuckin, Colin; Liu, Wai M.; Ball, Sarah E.; Gordon‐Smith, E. C.; Uhr, Mario

doi:10.1046/j.1365-2141.1996.d01-1493.x

Cited by 7 publications

(4 citation statements)

References 20 publications

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“…Separate experiments in stem cells harvested from the bone marrow of haematologically normal volunteers revealed that optimal colony formation was achieved using a SCF, IL-3, GM -CSF and EPO cocktail, consequently, all short-term cultures utilised this combination (McGuckin et al, 1996).…”

Section: Resultsmentioning

confidence: 99%

“…A hallmark of CML is the expansion of immature progenitor cells of the myeloid lineage in the bone marrow compartment, so that the majority of peripheral circulating CD34 + cells from CML patients are myeloid (Fialkow et al, 1977). PSCs were harvested from suspension cultures, washed and plated on semi-solid methylcellulose plates supplemented with a cocktail of GFs conducive to erythroid colony formation (McGuckin et al, 1996). Results were similar to those of Thiesing et al (2000), and showed that although there was a large number of cells seen on the culture plates, most lacked clonogenic capability since only a small number of colonies were seen.…”

Section: Molecular and Cellular Pathologymentioning

confidence: 99%

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The in vitro activity of the tyrosine kinase inhibitor STI571 in BCR–ABL positive chronic myeloid leukaemia cells: synergistic interactions with anti-leukaemic agents

2002

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Chronic myeloid leukaemia is typically characterised by the presence of dysregulated BCR -ABL tyrosine kinase activity, which is central to the oncogenic feature of being resistant to a wide range of cytotoxic agents. We have investigated whether the inhibition of this tyrosine kinase by the novel compound STI571 (formerly CGP57148B) would render K562, KU812 cell lines and chronic myeloid leukaemia-progenitor cells sensitive to induction of cell kill. Proliferation assays showed STI571 to be an effective cytotoxic agent in chronic myeloid leukaemia-derived cell lines (IC 50 on day 5 of 4.6 mg ml 71 and 3.4 mg ml 71 for K562 and KU812 respectively) and in leukaemic blast cells (per cent viability on day 3 at 4 mg ml 71 : 55.5+8.7 vs 96.4+3.7%). STI571 also appeared to specifically target bcr -abl expressing cells, as results from colony forming assays using the surviving cell fraction from STI571-treated peripheral CD34 + chronic myeloid leukaemia blast cells, indicated a reduction in the expansion of colonies of myeloid lineage, but no effect on normal colony formation. Our data also showed synergy between STI571 and other anti-leukaemic agents; as an example, there were significant increases in per cent cell kill in cell lines cultured with both STI571 and etoposide compared to the two alone (per cent cell kill on day 3: 73.7+11.3 vs 44.5+8.7 and 17.8+7.0% in cultures with STI571 and etoposide alone respectively; P50.001). This study confirms the central oncogenic role of BCR -ABL in the pathogenesis of chronic myeloid leukaemia, and highlights the role of targeting this tyrosine kinase as a useful tool in the clinical management of the disease.

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Section: Resultsmentioning

confidence: 99%

Section: Molecular and Cellular Pathologymentioning

confidence: 99%

The in vitro activity of the tyrosine kinase inhibitor STI571 in BCR–ABL positive chronic myeloid leukaemia cells: synergistic interactions with anti-leukaemic agents

2002

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“…In vitro a variable response to cytokines such as IL-3, SCF, GM-CSF and human recombinant erythropoietin has been demonstrated. 4,5 For patients who remain steroid-resistant the therapeutic options include regular transfusion therapy with chelation Correspondence: Dr RF Wynn, Royal Manchester Children's Hospital, Manchester, M27 4HA, UK Received 18 January 1999; accepted 13 May 1999 and stem cell transplantation. We report a case of failure of BMT to correct DBA, despite adequate engraftment.…”

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confidence: 99%

Failure of allogeneic bone marrow transplantation to correct Diamond–Blackfan anaemia despite haemopoietic stem cell engraftment

Wynn

Grainger

Carr

et al. 1999

Bone Marrow Transplant

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Summary:We report the case of a 10-year-old boy with congenital pure red cell aplasia (Diamond-Blackfan anaemia) who received an allogeneic bone marrow transplant (BMT) from his HLA-identical sister. The transplant was complicated by moderate veno-occlusive disease (VOD). Despite cytogenetic evidence of complete donor haemopoietic stem cell engraftment there was selective failure of red cell engraftment and he remains red cell transfusion-dependent. This is the first case of a stem cell transplant failing to correct the defect in this condition despite engraftment. Keywords: Diamond-Blackfan anaemia; bone marrow transplantation Diamond-Blackfan anaemia (DBA) is a congenital pure red cell aplasia usually presenting in the first year of life with profound normocytic or macrocytic anaemia, reticulocytopenia and marrow erythroblastopenia. It is a heterogenous condition with variable inheritance patterns, associated features and response to treatment.1 Although most cases are sporadic about 10% of cases are familial with either a dominant or recessive inheritance. Failure of spontaneous recovery and failure to demonstrate evidence of Parvovirus B19 distinguish DBA from transient erythroblastosis of childhood and red cell aplasia secondary to Parvovirus infection. Craniofacial anomalies, short stature and abnormalities of the thumb are the most commonly reported features.2 The location of the abnormal gene has been mapped in some cases of dominantly inherited DBA to chromosome 19q23. About 70% of cases are steroid-responsive and many of these will remain transfusion-independent although they often remain steroid-dependent. In vitro a variable response to cytokines such as IL-3, SCF, GM-CSF and human recombinant erythropoietin has been demonstrated. 4,5 For patients who remain steroid-resistant the therapeutic options include regular transfusion therapy with chelation Correspondence: Dr RF Wynn, Royal Manchester Children's Hospital, Manchester, M27 4HA, UK Received 18 January 1999; accepted 13 May 1999 and stem cell transplantation. We report a case of failure of BMT to correct DBA, despite adequate engraftment. Case report and methodsThe patient presented at 3. weeks of age with pallor following Caesarean section for foetal distress. There was no family history of DBA. His height was below the third centile but no physical anomalies were present. Blood count showed a Hb 6.1 with slight macrocytosis and mild thrombocythemia. There was no evidence of granular lymphocytosis on the blood film. Bone marrow aspirate showed erythroblastopenia with otherwise normal marrow. ELISA analysis for Parvovirus B19 was negative.He was transfusion-dependent from the age of 3 months and iron chelation, by subcutaneous desferrioxamine, was started at 20 months. There was no response to steroids or IL-3 and there were no red cell alloantibodies associated with red cell transfusion. Prior to BMT ferritin was recorded at 8200 g/l and liver biopsy showed marked iron deposition with no cirrhosis. Hepatitis and EBV serology was negative.He was...

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“…Blood chemistry studies showed raised levels of vitamin B12 ( I 340 pgldL), serum Fe (1 85 pg/dL), serum Fe and total iron-binding capacity (TIBC) ratio (185/197), and serum ferritin (514.5 ng/mL). Hb F was 19…”

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confidence: 99%

Transient erythrophagocytosis in Diamond‐Blackfan anemia

Sekine

Masuda

Kawamura

et al. 1997

Pediatrics International

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We report on a 4-month-old Japanese infant girl with Diamond-Blackfan anemia (DBA) as shown by congenital macrocytic pure red cell hypoplasia with marked reduction of erythroid precursors in bone marrow, reticulocytopenia, increased fetal hemoglobin, and elevated adenosine deaminase activity in peripheral blood. She responded poorly to conventional doses of corticosteroids, however, with high-dose corticosteroids she responded with reticulocytosis and an elevation of hemoglobin level above 12 g/dL. Erythrophagocytosis was noted during the tapering period of prednisone when her hemoglobin level declined to 7.6 g/dL and reticulocyte level to 0.4%. At that time, the erythrophagocytosis was noted in about 60% of marrow histiocytes. These findings were not observed prior to or during the high dose prednisone therapy. We speculate that one of the causes of pure red cell aplasia and reticulocytopenia in DBA is mediated by erythrophagocytosis.

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Diamond Blackfan anaemia: differential pattern of in vitro progenitor response to macrophage inflammatory protein 1‐alpha

Cited by 7 publications

References 20 publications

The in vitro activity of the tyrosine kinase inhibitor STI571 in BCR–ABL positive chronic myeloid leukaemia cells: synergistic interactions with anti-leukaemic agents

The in vitro activity of the tyrosine kinase inhibitor STI571 in BCR–ABL positive chronic myeloid leukaemia cells: synergistic interactions with anti-leukaemic agents

Failure of allogeneic bone marrow transplantation to correct Diamond–Blackfan anaemia despite haemopoietic stem cell engraftment

Transient erythrophagocytosis in Diamond‐Blackfan anemia

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