T Cell Lymphoblastic Leukemia with PICALM-MLLT10/t(10;11)(p13;q21) in a Fraction of Childhood ETP-ALL. -Molecular Study of Childhood T Cell Lymphoblastic Leukemia,
Authors: Kato Keisuke , Yoshimi Ai , Nakao Tomohei , Kobayashi Chie , Koike Kazutoshi , Kiyokawa Nobutaka , Tsuchida Masahiro 
Published: October 2019

Abstract
Abstract 3553

Background:
Although modern intensified protocol for childhood lymphoblastic leukemia has improved the prognosis of T lymphoblastic leukemia (T- ALL), significant proportion of patients with T-ALL succumbs to dismal outcome. Molecular and cytogenetic studies are important to precisely identify molecular marker to predict prognosis; however, the process is incomplete partly because of heterogeneity of molecular aspect in T-ALL. Recently combination of molecular and clinicopathological study have established early T cell precursor acute lymphoblastic leukemia (ETP-ALL) that has been proved to have poor prognosis. ETP-ALL is characterized by absence of CD1a and CD8 expression, weak CD5 expression, and expression of one or more myeloid or stem cell markers. However, ETP-ALL has been rarely defined on molecular aspect. During our cytogenetic and molecular investigation of cases with T-ALL, we have found that a proportion of ETP-ALL has PICALM-MLLT10 chimeric transcript.

Patients and Methods:
Using reverse transcription-polymerase chain reaction, we have investigated expression of PICALM-MLLT10, TLX1, TLX3, STIL-TAL1, MLL-MLLT1, and NUP214-ABL1 in fresh-frozen sample from twenty-two patients with T-ALL who had been treated in our institution. The cohort includes 2 cases with ETP-ALL. The clinical and cytogenetic features were also reviewed.

Result:
At the last follow-up, thirteen out of 22 patients were alive without the disease. Five patients succumbed to the recurrent disease and three patients died of complications. Furthermore, a patient having ETP-ALL is alive with recurrent disease. PICALM-MLLT10 chimeric transcript has been detected in four cases with T-ALL including a case with ETP-ALL with recurrent disease. The other three cases with PICALM-MLLT10 chimeric transcript are alive without the disease including two cases that underwent hematopoietic stem cell transplantation. STIL-TAL1 chimeric transcript has been confirmed in a case with T-ALL, who is alive without the disease. TLX1 transcript has been found in a case that succumbed to the disease, where karyotyping confirmed t(10;14)(q24;q11.2). Neither NUP214-ABL1 chimeric transcript, MLL-MLLT1 chimeric transcript, nor TLX3 transcript have been confirmed in cases investigated. The other ETP-ALL case has no specific chimeric transcript; however, karyotyping has revealed t(2;12)(q35;p13), where fluorescence in situ hybridization shows deletion but no translocation at ETV6 locus.

Conclusion:
This study provides the first evidence for that some ETP-ALL correspond to T-ALL with PICALM-MLLT10. Literature review has also shown that four out of 17 cases with ETP-ALL have chromosome abnormality at 10p13 or 11q21. Further investigation will be mandatory to molecularly define T-ALL, particularly ETP-ALL for providing the data to improve the prognosis by developing specifically targeted therapy.

Disclosures:
No relevant conflicts of interest to declare.