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.
We have presented the most significantly deregulated genes between cPTC and fvPTC: TMPRSS11, CEACAM6, ACTBL2, FN1, CRLF2, LDLR, LY6G6C, and TM7SF4 (Figure 2).
Similarly 8 gene expression markers differentiating between conventional and follicular variants of PTC were observed: TMPRSS11, CEACAM6, ACTBL2, FN1, CRLF2, LDLR, LY6G6C, and TM7SF4.
In addition, rs1054564 was associated with trans expression of the CRLF2 (cytokine receptor-like factor 2) gene, located on chromosome Xp22.
14] Human genes: GDF15, growth differentiation factor 15; PGPEP1, pyroglutamyl-peptidase I; LRRC25, leucine rich repeat containing 25; CRLF2, cytokine receptor-like factor 2; LRRC31, leucine rich repeat containing 31.
CRLF2 gene rearrangements were strongly associated with JAK2 mutations (10).
Harvey RC, Mullighan CG, Chen IM, Wharton W, Mikhail FM, Carroll AJ, Kang H, Liu W, Dobbin KK, Smith MA, Carroll WL, Devidas M, Bowman WP, Camitta BM, Reaman GH, Hunger SP, Downing JR, Willman CL: Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity and a poor outcome in pediatric B-progenitor acute lymphoblastic leukemia.
He noted the importance of increasing participation of adults in clinical trials as well as researching further potential prognostic indicators including molecular markers such as the IKZF1, JAK, and CRLF2
gene mutation as a marker for high-risk disease.
51,52) CRLF2 translocations have more recently been found in 7% to 14% of de novo B-ALL and 53% of Down syndrome-associated B-ALL.
Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia.
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.