Consistent quantitative gene product expression: #3. Invariance with age

Abstract

The quantitative expression of cell surface antigens and light scattering properties of five cellular reference populations in stressed bone marrow specimens were compared between pediatric and adult patients treated for acute myeloid leukemia (AML). The mean intensity of each antigen as well as the within patient and between patient variability showed striking consistency between the two different age groups. The only difference between the groups of specimens was the proportion of progenitor cells in the adult cohort averaged less than three times the proportion in the pediatric cohort. These data show that the amounts of gene products expressed on bone marrow cells are invariant with age. © 2016 The Authors. Cytometry Part A Published by Wiley Periodicals, Inc. on behalf of ISAC.

CD33 splicing SNP regulates expression levels of CD33 in normal regenerating monocytes in AML patients

“…The ratio in CD33 expression between the monocytes and leukemic blasts is similar to that observed in normal hematopoiesis between the uncommitted progenitor cells and monocytes (1,2). CD33 increases approximately 5X during maturation from the uncommitted progenitor cells to mature monocytes.…”

“…We have recently shown that the amounts of most gene products are precisely regulated during the development of hematopoietic cells in the bone marrow (1,2). Comparing the intensities of antigens (gene products) on cells of the same maturational stages, the variability within an individual exceeds that of the variability of the means between individuals.…”

“…The technique to determine mean fluorescence intensity (MFI) of CD33 on the leukemia cells (identified using CD45 and log side scatter gating) and on the mature monocytes on the corresponding regenerating marrow following induction chemotherapy (defined using support vector machines) have been described (3,10). Quantification of the expression of CD33 on mature monocytes was performed as described previously (1,2). Correlation of MFI to number of molecules was performed by defining the MFI of CD4 conjugated 1:1 to phycoerythrin to be 46,000 molecules (11,12).…”

High-dose AraC is essential for the treatment of ML-DS independent of postinduction MRD: results of the COG AAML1531 trial

“…Bone marrow samples were submitted at the end of the first course of induction therapy to a single central reference laboratory (Hematologics Inc, Seattle, WA) and stained with a standardized panel of monoclonal antibodies (supplemental Data), designed to detect residual disease by using the difference from normal approach (DN). [24][25][26][27][28][29] Specimens were processed as previously described. 24,25 Our analysis of ML-DS samples paid particular attention to avoiding misclassification of nonleukemic myeloid progenitors coexpressing CD56 and CD34, as well as CD33 (in addition to CD117, CD13, CD34, and CD45), which uniquely occur in regenerating normal bone marrow of children with DS after chemotherapy for AML or acute lymphoblastic leukemia, 30,31 as residual leukemic disease.…”

Phenotype in combination with genotype improves outcome prediction in acute myeloid leukemia: a report from Children’s Oncology Group protocol AAML0531

“…2 We recently reported that antigen intensity relationships of normal hematopoietic cell populations are invariant throughout maturation from an uncommitted progenitor cell to a mature blood cell among both pediatric and adult individuals. 3 , 4 The study helped confirm that with a high degree of quality control and system stability, 3 precise quantification of surface gene product expression can provide a robust basis to assess phenotypic deviations from normal maturation patterns that occur as a result of neoplastic transformation. 5 This concept is supported by our recent report of the recurrent multidimensional immunophenotype, RAM, which independently identifies high-risk pediatric AML at diagnosis.…”