Leukemias with these genetic profiles frequently demonstrate translocations of other tyrosine kinases, or alternatively have translocations involving the CRLF2 gene.
In addition, a CRLF2 rearrangement was observed in 51% of cells analyzed, and an extra IgH signal was present in 57% of cells, likely due to a translocation with CRLF2.
(15,16) The recent description of BCR-ABLl-like ALL (2,3) will probably result in an increase in future testing for other abnormalities associated with this poor-prognosis ALL type, such as CRLF2
translocations, which were uncommonly tested for in this survey.
This approach identified the "IL-7R network" which is comprised of the following proteins: IL2RG, IL-7, TSLP, CRLF2
, JAK1, and JAK3.
We have presented the most significantly deregulated genes between cPTC and fvPTC: TMPRSS11, CEACAM6, ACTBL2, FN1, CRLF2
, LDLR, LY6G6C, and TM7SF4 (Figure 2).
In Down syndrome, aberrant expression of CRLF2
is associated with mutated JAK2, suggesting that blocking the CRLF2/JAK2 pathway may be an effective method for Down syndrome therapy (8).
In addition, rs1054564 was associated with trans expression of the CRLF2
(cytokine receptor-like factor 2) gene, located on chromosome Xp22.3 (P = 1.61 X [10.sup.-11], and the LRRC31 (leucine rich repeat containing 31) gene, which is on chromosome 3q26.2 (P = 2.87 X [10.sup.-11]).
gene rearrangements were strongly associated with JAK2 mutations (10).
translocations have more recently been found in 7% to 14% of de novo B-ALL and 53% of Down syndrome-associated B-ALL.
In some ALL patients, chromosomal translocations create ABL1/NUP214 or P2RY8/ CRLF2
fusion proteins with oncogenic activity (41), (42).
Mutations in CRLF2
, IKZL1, TP53, ERG, and NOTCH have also been detected in precursor B and T lymphoblastic leukemia/lymphoblastic lymphoma and confer an adverse prognosis.