Differential expression of lymphoid and myeloid markers on differentiating hematopoietic stem cells in normal and tumor-bearing adult human liver

Golden-Mason, Lucy; Curry, Michael P.; Nolan, Niamh; Traynor, O.; McEntee, Gerry; Kelly, Jacinta; Hegarty, John E.; O’Farrelly, Cliona

doi:10.1053/jhep.2000.7713

Cited by 39 publications

(46 citation statements)

References 22 publications

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“…8,9,11,27,28 In patients with AML, there are likely to be CD33 ϩ leukemia cells in hepatic sinusoids 10 and CD33 ϩ hematopoietic cell precursor cells in the liver as part of extramedullary hematopoiesis. 29 We could not demonstrate a relation between leukocyte or blast counts in the circulation and development of sinusoidal obstruction syndrome in our patients, but it is possible that leukemia cells were sequestered in hepatic sinusoids out of proportion to peripheral blood blast counts. 10 There is no literature on the expression of CD33 on isolated human stellate cells, and immunohistochemistry studies of human liver tissue has not shown quiescent stellate cells to be CD33 ϩ .…”

Section: Org Fromcontrasting

confidence: 58%

Hepatic sinusoidal obstruction after gemtuzumab ozogamicin (Mylotarg) therapy

Rajvanshi

Shulman

Sievers

et al. 2002

Blood

225

125

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Gemtuzumab ozogamicin (Mylotarg) targets leukemia cells expressing the CD33 receptor by means of a monoclonal antibody conjugated to a cytotoxic agent, calicheamicin. Treatment of acute myeloid leukemia (AML) with gemtuzumab ozogamicin may result in liver injury. We reviewed the course of 23 patients who were given gemtuzumab ozogamicin for AML that had relapsed after hematopoietic cell transplantation. Liver toxicity was assessed through physical examination, serum tests, histologic examination, and hepatic venous pressure measurements. Liver injury developed in 11 patients after gemtuzumab ozogamicin administration; it was manifested as weight gain, ascites, and jaundice in 7 patients. Seven patients died with persistent liver dysfunction and either multiorgan failure or sepsis at a median of 40 days after gemtuzumab ozogamicin infusion. Portal pressure measurements were elevated in 2 patients. Results of liver histologic examination in 5 patients showed sinusoidal injury with extensive sinusoidal fibrosis, centrilobular congestion, and hepatocyte necrosis. Six patients experienced AML remission that was sustained for at least 60 days after gemtuzumab ozogamicin infusion. In summary, hepatic sinusoidal liver injury developed after gemtuzumab ozogamicin infusion. Histology showed striking deposition of sinusoidal collagen, suggesting that gemtuzumab ozogamicin targets CD33 ؉ cells residing in hepatic sinusoids as the mechanism for its hepatic toxicity. (Blood. 2002;99:2310-2314

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Section: Org Fromcontrasting

confidence: 58%

Hepatic sinusoidal obstruction after gemtuzumab ozogamicin (Mylotarg) therapy

Rajvanshi

Shulman

Sievers

et al. 2002

Blood

225

125

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“…2, less than half the CD34 ϩ population detected in both the EL and LP of the human intestine were of hemopoietic origin (coexpressed CD45). This is similar to what has been shown previously in the adult human liver (35). As our interest lay in hemopoietic progenitor cells, the CD34 ϩ CD45…”

Section: Discussionsupporting

confidence: 88%

“…It is possible that some of these differentiate from intestinal CD56 ϩ HSCs. The only other place in the body where large numbers of CD56 ϩ HSCs have been detected is the liver (34,35), another regional immune organ with significant populations of NKR ϩ T cells (36). Hepatic HSCs are similar to intestinal HSCs with respect to the coexpression of CD45RA, CD33, and CD56.…”

Section: Discussionmentioning

confidence: 99%

Detection and Characterization of Hemopoietic Stem Cells in the Adult Human Small Intestine

Lynch

O’Donoghue

Dean³

et al. 2006

The Journal of Immunology

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The concept of lymphoid differentiation in the human gastrointestinal tract is controversial but is the focus of this study, which examined adult human small intestinal tissue for the presence of CD34+CD45+ hemopoietic stem cells (HSCs) and lymphoid progenitors. Flow cytometry demonstrated that over 5% of leukocytes (CD45+ cells) isolated from human gut were HSCs coexpressing CD34, a significantly higher incidence than in matched peripheral blood or control bone marrow. HSCs were detected in cell preparations from both the epithelium and lamina propria of all samples tested and localized to the intestinal villous and crypt regions using immunofluorescence. A high proportion of gut HSCs expressed the activation marker CD45RA, and few expressed c-kit, indicating ongoing differentiation. The vast majority of intestinal HSCs coexpressed the T cell Ag, CD7 (92% in the epithelium, 80% in the lamina propria) whereas <10% coexpressed the myeloid Ag CD33, suggesting that gut HSCs are a relatively mature population committed to the lymphoid lineage. Interestingly, almost 50% of epithelial layer HSCs coexpressed CD56, the NK cell Ag, compared with only 10% of the lamina propria HSC population, suggesting that the epithelium may be a preferential site of NKR+ lymphoid differentiation. In contrast, bone marrow HSCs displayed low coexpression of CD56 and CD7 but high coexpression of CD33. The phenotype of intestinal HSCs, which differs significantly from circulating or bone marrow HSCs, is consistent with a role in local lymphoid development.

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“…on May 11, 2018. by guest www.bloodjournal.org From hematopoiesis in human liver grafts and extramedullary hematopoiesis from liver in cases of severe marrow failure 8,9,38 raise the alternate possibility that HSCs of the adult liver may participate in hematopoiesis in situ.…”

Section: Discussionmentioning

confidence: 99%