Homo sapiens diseases - T-cell acute lymphoblastic leukemia (T-ALL)

HOMO SAPIENS DISEASES - T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (T-ALL)

Table of contents :

Epidemiology

Aetiology

Pathogenesis

Symptoms & signs

Laboratory examinations

Differential diagnosis

Therapy

Prognosis

Web resources

Epidemiology : it is more common in males than in females and affects children and adults equally; 20% of all ALLs; 10%-15% of pediatric and 25% of adult ALL cases; L1 or L2
Pathogenesis : translocations involving

LMO2 (t(11;14)(p13;q32)) : present at strikingly high frequency in normal human thymus, and that the recombinogenic potential conferred by the LMO2 cryptic site is directly predictive of the in vivo level of translocation at that locus^ref
TAL1/SCL gene is frequently activated in T-ALL patients and induces leukemia by silencing E47/HEB / TCF12 gene (a TF for many different genes required for immune cell differentiation and survival) expression by recruiting a HDAC. HDAC inhibitors may prove efficacious in T-ALL patients who express TAL1/SCL
TAL2

... are compatible with illegitimate V(D)J recombination between a TcR locus and a proto-oncogene locus bearing a fortuitous but functional recombination site. Transcription factors are known to be deregulated by chromosomal translocations, but mutations in protein tyrosine kinases have only rarely been identified. The extrachromosomal (episomal) amplification of ABL1, an aberration that is not detectable by conventional cytogenetics, occurs in 5.6% of individuals with T-ALL. Molecular analyses delineated the amplicon as a 500-kb region from chromosome band 9q34, containing the fusion between oncogenes ABL1 and NUP214. The constitutively phosphorylated tyrosine kinase NUP214-ABL1 is sensitive to the tyrosine kinase inhibitor imatinib. The recurrent cryptic NUP214-ABL1 rearrangement is associated with increased HOX expression and deletion of CDKN2A 9, consistent with a multistep pathogenesis of T-ALL^ref. Very rare cases of human T-ALL harbor chromosomal translocations that involve NOTCH1

, a gene encoding a transmembrane receptor that regulates normal T cell development, but > 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain of NOTCH1^ref.
Laboratory examinations :

immunophenotype : CD7⁺, TcR⁺

T1 (pro-T) : CD1a^-2^-3^+/-4^-, cCD3⁺, TdT⁺
T2 (pre-T) : CD1a^-2^+/-3⁺4^-, cCD3^+/-, TdT^+/-
T3 (cortical T) : CD1a⁺2⁺3⁺4⁺, cCD3^-, TdT^+/-
T4 (mature T) : CD1a^-2⁺3⁺4⁺, cCD3^-, TdT^-