An article published this year in “JOURNAL OF HEMATOLOGY & ONCOLOGY”
using our PE-Cyanine7 anti-CD19, by our customers
from Servicio de Hematología & IBSAL, IBMCC, CIC Universidad de
Salamanca-CSIC, Hospital Universitario, in the analysis of how Next-generation
sequencing and FISH studies reveal the appearance of gene mutations and
chromosomal abnormalities in hematopoietic progenitors in chronic lymphocytic
leukemia. Congrats and Thanks.
Summary:
Background
Chronic lymphocytic leukemia (CLL) is a highly
genetically heterogeneous disease. Although CLL has been traditionally
considered as a mature B cell leukemia, few independent studies have shown that
the genetic alterations may appear in CD34+ hematopoietic progenitors. However,
the presence of both chromosomal aberrations and gene mutations in CD34+ cells
from the same patients has not been explored.
Methods
Amplicon-based deep next-generation sequencing
(NGS) studies were carried out in magnetically activated-cell-sorting separated
CD19+ mature B lymphocytes and CD34+ hematopoietic progenitors (n = 56) to
study the mutational status of TP53, NOTCH1, SF3B1, FBXW7, MYD88, and XPO1
genes. In addition, ultra-deep NGS was performed in a subset of seven patients
to determine the presence of mutations in flow-sorted CD34+CD19− early
hematopoietic progenitors. Fluorescence in situ hybridization (FISH) studies were
performed in the CD34+ cells from nine patients of the cohort to examine the
presence of cytogenetic abnormalities.
Results
NGS studies revealed a total of 28 mutations
in 24 CLL patients. Interestingly, 15 of them also showed the same mutations in
their corresponding whole population of CD34+ progenitors. The majority of
NOTCH1 (7/9) and XPO1 (4/4) mutations presented a similar mutational burden in
both cell fractions; by contrast, mutations of TP53 (2/2), FBXW7 (2/2), and
SF3B1 (3/4) showed lower mutational allele frequencies, or even none, in the
CD34+ cells compared with the CD19+ population. Ultra-deep NGS confirmed the
presence of FBXW7, MYD88, NOTCH1, and XPO1 mutations in the subpopulation of
CD34+CD19− early hematopoietic progenitors (6/7). Furthermore, FISH studies
showed the presence of 11q and 13q deletions (2/2 and 3/5, respectively) in
CD34+ progenitors but the absence of IGH cytogenetic alterations (0/2) in the
CD34+ cells. Combining all the results from NGS and FISH, a model of the appearance
and expansion of genetic alterations in CLL was derived, suggesting that most
of the genetic events appear on the hematopoietic progenitors, although these
mutations could induce the beginning of tumoral cell expansion at different
stage of B cell differentiation.
Conclusions
Our study showed the presence of both gene
mutations and chromosomal abnormalities in early hematopoietic progenitor cells
from CLL patients.
Reference:
Product link:
PE-Cyanine7 - anti Human CD19 - HIB19: http://www.immunostep.com/cd-antibodies/2765-cd19.html
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