Functional pathway analysis in acute myeloid leukemia using single cell network profiling assay: Effect of specimen source (bone marrow or peripheral blood) on assay readouts

Alessandra Cesano, David B. Rosen, Pat O'Meara, Santosh Putta, Urte Gayko, David C. Spellmeyer, Larry D. Cripe, Zhuoxin Sun, Hajime Uno, Mark R Litzow, Martin S. Tallman, Elisabeth Paietta

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Single cell network profiling (SCNP) is used to simultaneously measure the effects of modulators on signaling networks at the single cell level. SCNP-based biomarker assays predictive of response to induction therapy and relapse risk in acute myeloid leukemia (AML) patients are being developed. Such assays have typically used bone marrow (BM) as the sample source of blasts. Because circulating peripheral blasts are detectable in ∼65% of AML patients and peripheral blood (PB) sampling is less invasive than BM sampling, this study was performed to assess the effect of sample source on AML blasts signaling as measured in SCNP assay. Methods: SCNP using multiparametric flow cytometry was used to evaluate the activation state of intracellular signaling molecules in leukemic blasts under basal conditions and after treatment with modulators in 46 pairs of BM mononuclear cells/PB mononuclear cells. The relationship between readouts of modulated intracellular proteins ("nodes") was measured using linear regression, Bland-Altman method, and Lin's concordance correlation coefficient. Results: The majority (156/161) of signaling nodes show strong correlations between paired PB and BM samples independently from the statistical method used. Notable exceptions were two PB samples with almost undetectable levels of circulating blasts compared with paired BM samples. Conclusions: Our results demonstrate that specimen source (BM or PB) does not significantly affect proteomic signaling in patients with AML and circulating blasts. The ability to use PB as a sample source will facilitate the monitoring of cellular signaling effects following administration of targeted therapies and at time points when BM aspirates are not clinically justifiable.

Original languageEnglish (US)
Pages (from-to)158-172
Number of pages15
JournalCytometry Part B - Clinical Cytometry
Volume82 B
Issue number3
DOIs
StatePublished - May 2012

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Acute Myeloid Leukemia
Bone Marrow
Sampling Studies
Bone Marrow Cells
Proteomics
Linear Models
Blood Cells
Flow Cytometry
Therapeutics
Biomarkers
Recurrence
Proteins

Keywords

  • acute myeloid leukemia
  • cell signaling
  • diagnostic
  • flow cytometry
  • multiparameter analysis
  • single cell network profiling
  • specimen source
  • standardization

ASJC Scopus subject areas

  • Cell Biology
  • Histology
  • Pathology and Forensic Medicine

Cite this

Functional pathway analysis in acute myeloid leukemia using single cell network profiling assay : Effect of specimen source (bone marrow or peripheral blood) on assay readouts. / Cesano, Alessandra; Rosen, David B.; O'Meara, Pat; Putta, Santosh; Gayko, Urte; Spellmeyer, David C.; Cripe, Larry D.; Sun, Zhuoxin; Uno, Hajime; Litzow, Mark R; Tallman, Martin S.; Paietta, Elisabeth.

In: Cytometry Part B - Clinical Cytometry, Vol. 82 B, No. 3, 05.2012, p. 158-172.

Research output: Contribution to journalArticle

Cesano, Alessandra ; Rosen, David B. ; O'Meara, Pat ; Putta, Santosh ; Gayko, Urte ; Spellmeyer, David C. ; Cripe, Larry D. ; Sun, Zhuoxin ; Uno, Hajime ; Litzow, Mark R ; Tallman, Martin S. ; Paietta, Elisabeth. / Functional pathway analysis in acute myeloid leukemia using single cell network profiling assay : Effect of specimen source (bone marrow or peripheral blood) on assay readouts. In: Cytometry Part B - Clinical Cytometry. 2012 ; Vol. 82 B, No. 3. pp. 158-172.
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AU - Cesano, Alessandra

AU - Rosen, David B.

AU - O'Meara, Pat

AU - Putta, Santosh

AU - Gayko, Urte

AU - Spellmeyer, David C.

AU - Cripe, Larry D.

AU - Sun, Zhuoxin

AU - Uno, Hajime

AU - Litzow, Mark R

AU - Tallman, Martin S.

AU - Paietta, Elisabeth

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N2 - Background: Single cell network profiling (SCNP) is used to simultaneously measure the effects of modulators on signaling networks at the single cell level. SCNP-based biomarker assays predictive of response to induction therapy and relapse risk in acute myeloid leukemia (AML) patients are being developed. Such assays have typically used bone marrow (BM) as the sample source of blasts. Because circulating peripheral blasts are detectable in ∼65% of AML patients and peripheral blood (PB) sampling is less invasive than BM sampling, this study was performed to assess the effect of sample source on AML blasts signaling as measured in SCNP assay. Methods: SCNP using multiparametric flow cytometry was used to evaluate the activation state of intracellular signaling molecules in leukemic blasts under basal conditions and after treatment with modulators in 46 pairs of BM mononuclear cells/PB mononuclear cells. The relationship between readouts of modulated intracellular proteins ("nodes") was measured using linear regression, Bland-Altman method, and Lin's concordance correlation coefficient. Results: The majority (156/161) of signaling nodes show strong correlations between paired PB and BM samples independently from the statistical method used. Notable exceptions were two PB samples with almost undetectable levels of circulating blasts compared with paired BM samples. Conclusions: Our results demonstrate that specimen source (BM or PB) does not significantly affect proteomic signaling in patients with AML and circulating blasts. The ability to use PB as a sample source will facilitate the monitoring of cellular signaling effects following administration of targeted therapies and at time points when BM aspirates are not clinically justifiable.

AB - Background: Single cell network profiling (SCNP) is used to simultaneously measure the effects of modulators on signaling networks at the single cell level. SCNP-based biomarker assays predictive of response to induction therapy and relapse risk in acute myeloid leukemia (AML) patients are being developed. Such assays have typically used bone marrow (BM) as the sample source of blasts. Because circulating peripheral blasts are detectable in ∼65% of AML patients and peripheral blood (PB) sampling is less invasive than BM sampling, this study was performed to assess the effect of sample source on AML blasts signaling as measured in SCNP assay. Methods: SCNP using multiparametric flow cytometry was used to evaluate the activation state of intracellular signaling molecules in leukemic blasts under basal conditions and after treatment with modulators in 46 pairs of BM mononuclear cells/PB mononuclear cells. The relationship between readouts of modulated intracellular proteins ("nodes") was measured using linear regression, Bland-Altman method, and Lin's concordance correlation coefficient. Results: The majority (156/161) of signaling nodes show strong correlations between paired PB and BM samples independently from the statistical method used. Notable exceptions were two PB samples with almost undetectable levels of circulating blasts compared with paired BM samples. Conclusions: Our results demonstrate that specimen source (BM or PB) does not significantly affect proteomic signaling in patients with AML and circulating blasts. The ability to use PB as a sample source will facilitate the monitoring of cellular signaling effects following administration of targeted therapies and at time points when BM aspirates are not clinically justifiable.

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