T-cell acute lymphoblastic leukemia (T-ALL) predominantly in children > 5 years-old, which accounts for approximately 15% of pediatric ALL in age range. Recent studies demonstrated that an accumulation of chromosomal rearrangements and other genetic anomalies is necessary for T-ALL development. However causal factors and time latency for childhood T-ALL remains enigmatic. Unlike B-cell precursor ALL that involves genetic events prenatally or in early infancy, T-ALL early childhood have controversial results regarding prenatal origin. Therefore, we conducted a molecular screening in infants with T-ALL searching for the most common genetic markers associated with this malignancy. This series of cases was selected from the incident cases included in the Brazilian Collaborative Study for IAL. The diagnosis of T-ALL was made according to morphology and EGIL classification, followed by conventional karyotyping. Sixteen cases of T-ALL IL were analyzed either by PCR-RFLP (FLT3), RT-PCR (MLL, SIL/TAL1 and HOX11L2) or PCR-DHPLC (NOTCH1), tracing the genetic alterations commonly found in these genes. Mean age at diagnosis was 14.6 months (6–24), there was a predominance of high white blood cells (WBC) count, and a poor survival in this series of cases. Cytogenetic aberrations included del(12p) (#2), t(11;14) (#3), del(6)(q23) and del(7) (q32) (#11), and 49, XY,+6,+8,+19 (#15). Details of all molecular markers are presented in Table. Then molecular markers were identified in 8 out of 16 (50%) T-ALL cases. The observed markers included MLL rearrangements (n=2), FLT3-ITD (n=1), SIL/TAL1 (n=2), HOX11L2 (n=1), and NOTCH1 (n=4). SIL/TAL1 and NOTCH1 abnormalities were found concomitantly in one case (#7) in the diagnostic sample. By the fact that the onset of T-ALL arose in a short time latency from birth to diagnosis we suggested that T-ALL might originate prenatally in these cases.

Table. Laboratorial and Molecular Features of Patients

IDAge(months)GenderWBC(×109/L)EGILMLLFLT3SIL/TAL1HOX11L2NOTCH1Outcome
#1 24 F 86.0 T-I Neg WT Neg Neg WT Dead 
#2 20 F 240.1 T-I Neg WT Neg Neg WT Dead 
#3 22 M 380.1 T-II Neg ITD Pos Neg WT Dead 
#4 24 M 440.1 T-IV Neg WT Neg Neg WT Dead 
#5 20 F 330.0 T-IV Pos1 WT Neg Neg WT Alive 
#6 12 M 80.1 T-IV Neg WT Neg Neg WT Dead 
#7 13 F 71.3 T-I Neg WT Pos Neg Mut Lost 
#8 9 M 56.2 T-IV Neg WT Neg Neg Mut Alive 
#9 14 M 57.1 T-IV Neg WT Pos Neg WT Lost 
#10 7 M 110.0 T-IV Pos2 WT Neg Neg WT Alive 
#11 17 M 180.1 T-I Neg WT Neg Neg WT Alive 
#12 20 F 78.6 T-I Neg WT Neg Neg WT Dead 
#13 9 M 71.0 T-IV Neg WT Neg Neg WT Dead 
#14 9 F 50.0 NA Neg WT Neg Neg Mut Dead 
#15 8 M 154.0 T-IV Neg WT Neg Neg Mut Alive 
#16 6 F 131.6 T-IV Neg WT Neg Pos WT Alive 
IDAge(months)GenderWBC(×109/L)EGILMLLFLT3SIL/TAL1HOX11L2NOTCH1Outcome
#1 24 F 86.0 T-I Neg WT Neg Neg WT Dead 
#2 20 F 240.1 T-I Neg WT Neg Neg WT Dead 
#3 22 M 380.1 T-II Neg ITD Pos Neg WT Dead 
#4 24 M 440.1 T-IV Neg WT Neg Neg WT Dead 
#5 20 F 330.0 T-IV Pos1 WT Neg Neg WT Alive 
#6 12 M 80.1 T-IV Neg WT Neg Neg WT Dead 
#7 13 F 71.3 T-I Neg WT Pos Neg Mut Lost 
#8 9 M 56.2 T-IV Neg WT Neg Neg Mut Alive 
#9 14 M 57.1 T-IV Neg WT Pos Neg WT Lost 
#10 7 M 110.0 T-IV Pos2 WT Neg Neg WT Alive 
#11 17 M 180.1 T-I Neg WT Neg Neg WT Alive 
#12 20 F 78.6 T-I Neg WT Neg Neg WT Dead 
#13 9 M 71.0 T-IV Neg WT Neg Neg WT Dead 
#14 9 F 50.0 NA Neg WT Neg Neg Mut Dead 
#15 8 M 154.0 T-IV Neg WT Neg Neg Mut Alive 
#16 6 F 131.6 T-IV Neg WT Neg Pos WT Alive 
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Abbreviations: F, female; M, male; WBC, white blood cells count; NA, not available; Neg, negative; Pos, positive; WT, wild-type; ITD, internal tandem duplication; Mut, mutated; 1MLL/AF4; 2MLL/ENL.

Topics:
adult t-cell lymphoma/leukemia, biological markers, cancer, child, impedance threshold device, karyotype determination procedure, leukemia, lymphocytic, acute, childhood, lymphoblastic leukemia, ms-like tyrosine kinase 3, polymerase chain reaction

Disclosures: No relevant conflicts of interest to declare.

Author notes

Corresponding author

2008, The American Society of Hematology
2008
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