Figure 7
Figure 7. Distinct expression pattern of the HOXA and -B cluster genes in pediatric AML with NUP98/NSD1. (A) Principal component analysis of pediatric AML subgroups characterized by specific type-II aberrations (n = 210) was carried out based on all HOXA and –B–annotating probe sets present on the HGU133 Plus 2.0 microarray (Affymetrix). Each color-coded circle represents an individual AML case. Three distinct groups are observed in the principal component analysis, which are indicated by the white circles. (B) Heat map showing the expression of all HOXA and B-annotating probe sets in which the cells represent relative log 2 expression values and are color-coded on a scale ranging from bright green (−2) to bright red (+2), with black indicating no change relative to the median. The pediatric AML cases are grouped together based on their specific type-II aberration as indicated by the color-coded bars below the heat map, and the probe sets are alphabetically ordered. Three groups with distinct expression patterns are observed, that is, group 1, characterized by low or absent expression of HOXA and -B genes; group 2, characterized by solely high expression of HOXA genes (mainly HOXA5-A10); and group 3, characterized by expression of both HOXA and -B genes (mainly HOXA5-A10 and HOXB2-B6). The latter included the NUP98/NSD1 cases. (C) Variance stabilization and normalization (VSN)–normalization-normalized expression levels of HOX-annotating probe sets A5, A7, A9,and A10 and B2, B3, B4, B5, and B6 and a probe set annotating MEIS1 were depicted per graph for all pediatric AML cases (n = 274) grouped by their specific type-II aberration. NUP98/NSD1 cases were characterized by high HOXA9, -A10, -B2, -B3, -B4, -B5, -B6, and MEIS1 expression. (D) Relative expression levels of miRNA-10a and -196b by stem-loop qRT-PCR in pediatric AML cases (n = 90 and n = 84, respectively), representing the different genetic subgroups in pediatric AML. Both miRNA-10a and -196b are highly expressed in the group 3-members, whereas only miRNA-196b, but not miRNA-10a is highly expressed in the majority of the MLL-rearranged cases, correlating exactly with HOXA and -B expression, respectively.

Distinct expression pattern of the HOXA and -B cluster genes in pediatric AML with NUP98/NSD1. (A) Principal component analysis of pediatric AML subgroups characterized by specific type-II aberrations (n = 210) was carried out based on all HOXA and –B–annotating probe sets present on the HGU133 Plus 2.0 microarray (Affymetrix). Each color-coded circle represents an individual AML case. Three distinct groups are observed in the principal component analysis, which are indicated by the white circles. (B) Heat map showing the expression of all HOXA and B-annotating probe sets in which the cells represent relative log 2 expression values and are color-coded on a scale ranging from bright green (−2) to bright red (+2), with black indicating no change relative to the median. The pediatric AML cases are grouped together based on their specific type-II aberration as indicated by the color-coded bars below the heat map, and the probe sets are alphabetically ordered. Three groups with distinct expression patterns are observed, that is, group 1, characterized by low or absent expression of HOXA and -B genes; group 2, characterized by solely high expression of HOXA genes (mainly HOXA5-A10); and group 3, characterized by expression of both HOXA and -B genes (mainly HOXA5-A10 and HOXB2-B6). The latter included the NUP98/NSD1 cases. (C) Variance stabilization and normalization (VSN)–normalization-normalized expression levels of HOX-annotating probe sets A5, A7, A9,and A10 and B2, B3, B4, B5, and B6 and a probe set annotating MEIS1 were depicted per graph for all pediatric AML cases (n = 274) grouped by their specific type-II aberration. NUP98/NSD1 cases were characterized by high HOXA9, -A10, -B2, -B3, -B4, -B5, -B6, and MEIS1 expression. (D) Relative expression levels of miRNA-10a and -196b by stem-loop qRT-PCR in pediatric AML cases (n = 90 and n = 84, respectively), representing the different genetic subgroups in pediatric AML. Both miRNA-10a and -196b are highly expressed in the group 3-members, whereas only miRNA-196b, but not miRNA-10a is highly expressed in the majority of the MLL-rearranged cases, correlating exactly with HOXA and -B expression, respectively.

Close Modal
This Feature Is Available To Subscribers Only

or Create an Account

Close Modal
Close Modal