Mutations in genes regulating lymphoid development are a hallmark of ALL, and alterations of the lymphoid transcription factor gene IKZF1 (IKAROS) are associated with a high risk of treatment failure in B-ALL.
Aberrant expression of tumor suppressor genes WT 1, RB 1, p53, homozygous deletion of p16 gene and their relationship with expression of oncogenes BCR-ABL, TEL-AML 1, MLL-AF 4, E2A-PBX 1, SIL-TAL 1 were determined in bone marrow samples of children with de novo B-lineage (n=170) and T-lineage (n=25) acute lymphoblastic leukemia (ALL).
These findings suggest that, in ALL leukemogenesis, loss of CDKN2A and other target genes in the instability region is frequently associated with BCR/ABL1 and IKZF1 dysfunction.
In ALL an association of homozygous deletions of p16ink4a and p15ink4b, and T-lineage, 9p abnormalities, and prognostic factors was found in some but not all reports.
The IKZF1 SNPs, rs10235796 and rs6964969, and the CDKN2A SNP rs3731246 (previously unreported) could serve as risk markers for ALL susceptibility in Yemeni children.
Six of 12 cell lines, including acute lymphoblastic leukemia (ALL) lines of T-cell (three of four), of precursor-B cell (two of four) and of mixed phenotype (one of four), showed homozygous deletion of the p16 gene using PCR and Southern blotting.
In addition, IKZF1 has been implicated in roles involved in some hematologic traits or abnormalities, such as erythrocyte measures, myelofibrosis, and acute lymphoblastic leukemia (ALL), which may be common clinical manifestations or co-occurrence hematological diseases of patients with SLE.
We analyzed p16INK4A and p15INK4B genes in 178 cases of primary leukemias including 81 cases of chronic lymphocytic leukemia (CLL), seven of hairy cell leukemia (HCL), seven of chronic myelogenous leukemia (CML), 43 of acute myelogenous leukemia (AML), 27 of acute lymphoblastic leukemia (ALL), and 13 of myelodysplastic syndrome (MDS) by Southern blot analyses.
The methylation-specific polymerase chain reaction (MS-PCR) was used to analyze p15 and p16 gene methylation in 49 cases of acute lymphoblastic leukemia (ALL) and 29 cases of acute myelogenous leukemia (AML).
Philadelphia chromosome-like ALL is essentially heterogeneous; however, deletion mutations in the IKZF1 gene encoding the transcription factor IKAROS underlie many cases as a key factor inducing aggressive phenotypes and poor treatment responses.
Previous studies have shown evidence for association between risk of ALL and variation within IKZF1, ARID5B, CEBPE, CDKN2A, GATA3, and BM1-PIP4K2A genes.
We therefore analyzed the clinical and biological implications of this feature by studying p16ink4a expression in 58 cases of childhood ALL. mRNA and protein were significantly correlated and both appeared more highly expressed in B than in T lineage ALLs: 13 out of the 15 T cell ALLs did not show any p16ink4a expression.
<i>CDKN2A/2B</i> deletions were associated with poor 2-year OS (P=0.045) and RFS (P=0.071) rates in Philadelphia chromosome positive (Ph<sup>+</sup>) B-ALL patients, as well as in the high risk (HR) B-ALL group (P=0.037 and P=0.047, respectively).
The multiplex ligation-dependent probe amplification (MLPA) method was used to detect the copy number alterations (CNAs) of IKAROS family zinc finger 1 (<i>IKZF1</i>), paired box 5 (<i>PAX5</i>), ETS variant 6 (<i>ETV6</i>), RB transcriptional corepressor 1 (<i>RB1</i>), BTG anti-proliferation factor 1 (<i>BTG1</i>), early B-cell factor 1 (<i>EBF1</i>), cyclin dependent kinase inhibitor 2A/2B (<i>CDKN2A/2B</i>) and cytokine receptor like factor 2 (<i>CRLF2</i>) genes in 87 adults with acute lymphoblastic leukemia (ALL) in China.
Recurrent deletions of the CDKN2A/ARF/CDKN2B genes encoded at chromosome 9p21 have been described in both pediatric and adult acute lymphoblastic leukemia (ALL), but their prognostic value remains controversial, with limited data on adult T-ALL.
Notably, genetic alteration of the lymphoid transcription factor gene IKZF1 is a hallmark of multiple subtypes of ALL with poor prognosis, including BCR-ABL1-positive lymphoid leukemia and a subset of 'BCR-ABL1-like' ALL cases that, in addition to IKZF1 alteration, harbor genetic mutations resulting in aberrant lymphoid cytokine receptor signaling, including activating mutations of Janus kinases and rearrangement of cytokine receptor-like factor 2 (CRLF2).
To address this issue, we determined whether the CDKN2 gene deletions found in acute lymphoblastic leukemia (ALL) cell lines are also detected in the primary leukemia samples.
Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica-Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22.33/Yp11.31 (PAR1 region; CRLF2, CSF2RA, and IL3RA), and ERG; replication of findings involved 417 patients from the same trial.