Acute Leukemias - Republican Scientific Medical Library

Molecular Biology and Genetics
Meir Wetzler, Mrózek Kryzstof
Contents
6.1 Introduction .................... 95
6.2 Cytogenetic Aberrations ........... 95
6.3 Structural Aberrations ............. 96
6.3.1 t(9;22)(q34;q11.2) ............ 96
6.3.2 MLL Gene Rearrangements ..... 96
6.3.3 t(4;11)(q21;q23) ............. 97
6.3.4 del(9p) or t(9p) .............. 97
6.3.5 del(12p) or t(12p) ............ 98
6.3.6 t(14q11-q13) ............... 98
6.3.7 Translocations Involving
Band (14q32) Other than
t(8;14)(q24;q32) ............. 99
6.3.8 del(6q) .................... 99
6.3.9 t(1;19)(q23;p13) ............. 99
6.3.10 Extrachromosomal Amplification
of the NUP214/ABL Fusion Gene
in T-Cell ALL ................ 99
6.4 Numerical Aberrations ............ 100
6.4.1 High Hyperdiploidy ........... 100
6.4.2 Hypodiploidy ............... 100
6.4.3 Trisomy 8 .................. 101
6.4.4 Monosomy 7 ............... 101
6.5 Molecular Aberrations ............ 101
6.5.1 Relapse-Classifying Gene Sets .... 101
6.5.2 Resistance-Classifying Gene Sets . . 101
6.5.3 Smad3 .................... 101
6.5.4 FLT3 ..................... 102
6.5.5 TLX1 ..................... 102
6.5.6 Cryptic t(5;14)(q35;q32) and the
Overexpression of the TLX3 Gene 102
6.5.7 NOTCH1 .................. 102
6.5.8 Pharmacogenetics ........... 102
6.6 Future Directions ................ 103
References ......................... 103
6.1 Introduction
Acute lymphoblastic leukemia (ALL) is characterized by
distinctive morphologic, cytogenetic, and molecular genetic
features, some of which have important clinical
implications for both diagnosis and predicting response
to specific treatment regimens, while the role of others
is yet to be defined. This chapter will describe the cytogenetic
and molecular aberrations in ALL.
6.2 Cytogenetic Aberrations
Cytogenetic aberrations can be structural, e.g., reciprocal
and unbalanced translocations, deletions, dicentric
chromosomes, or inversions; or numerical, e.g., gain
of a whole chromosome (trisomy) or loss of a whole
chromosome (monosomy). In many instances, molecular
dissection of structural chromosome abnormalities,
especially reciprocal translocations, identified specific
genes associated with leukemogenesis. The most common
structural cytogenetic aberrations and their affected
genes are shown in Table 6.1.