Chromosomal translocations in hematological malignancies

In several neoplastic entities, the development of a malignant phenotype has been intimately related to the gain of abnormal chromosomal patterns. Chronic myelogenous leukemia is the first disease in which an association with a consistent chromosomal abnormality (chromosome Philadelphia) was established. This results from a reciprocal translocation involving chromosomes 9 and 22. Subsequently, this translocation was also shown to occur in acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) at low frequencies. The consequence of this t(9;22) is the expression of a chimeric protein that contains sequences from both the partner genes c-ABL (9) and BCR (22).

As can be seen in Table 1, the list of nonrandom chromosomal abnormalities in hematological malignancies has grown significantly. Several points can be made from cytogenetic correlations. In most cases there is a high specificity between the morphological classification and the presence of a given abnormality, e.g. the t(14;18) is specifically observed in follicular lymphomas. A more impressive correlation is the restricted involvement of chromosomal loci that harbor immune genes: 2pl2, 7q34, 14qll, 14q32 and 22qll in tumors of lymphoid lineage rather than

Table 1 The most frequent nonrandom chromosomal translocations in hematological neoplasms

Translocation Genes involved Neoplasms t(1;7)(p32;q34)

t(11;14)(q23;q32) t(11;17)(q23;q21) t(11;17)(q23;q21) t(11;19)(q23;p13) t(11;22)(q13;q11) t(14;14)(q11;q32) t(14;18)(q32;q21) t(14;19)(q32;q13) t(15;17)(q22;q11) t(16;16)(p13;q22) t(16;21)(p11;q22) t(17;19)(q22;p13) t(18;22)(q21;q11) t(X;11)(q13;q23)

SCL; TCRß LCK; TCRß AF-1P; MLL SCL; TCRR PBX-1 ; E2A Ig-K; Bcl-6 ALK; NPM lg-K; MYC Ig «; Bcl-2 EVI-1 ; ? MLF1; NPM Bcl-6; IgH EVI-1 ; AML-1 Bcl-6; Ig-X AF-4/FEL; MLL PDGFRß; TEL IL-3; IgH NPM; RARa DEK;CAN AF-6; MLL TCRß; TAL-2 TCRß; TAN-1 TCRß; HOX-11 TCRß; RBTN-2 TCRß; LYL-1 MYC; TCR« MYC; IgH ETO; AML-1 MYC; Ig-X AF-9; MLL ABL; BCR AF-10; MLL HOX-11; TCRS LYT-10; IgH RBTN-2; TCR8 RBTN-1; TCRS BCL-1 ; IgH

MLL: IgH MLL; AF-17 PLZF; RARa MLL; ENL Bcl-1, Ig-X TCRa; TCL-1 IgH; Bcl-2 IgH; Bcl-3 PML; RARa MYH11; CBFB TLS; ERG HLF; E2A Bcl-2; Ig-X AFX1; MLL

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