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186 Part IV: Molecular and Cellular Hematology Chapter 13: Cytogenetics and Genetic Abnormalities 187

Figure 13–5. Partial karyotypes of trypsin-
Giemsa-banded metaphase cells depicting recur-
ring chromosomal rearrangements observed in
lymphoid malignant diseases. The rearranged
chromosomes are identified with arrows. A. t(4;11)
(q21.3;q23.3) in ALL. B. t(1;19)(q23;p13.3) in pre-B
cell ALL. C. t(8;14)(q24.2;q32) in B-cell ALL and
Burkitt lymphoma. D. inv(14)(q11.2q32.1) in T-cell
leukemia/lymphoma. E. t(8;14)(q24.2;q11.2) in
A B C T-cell leukemia/lymphoma. F. t(14;18)(q32.3;q21.3)
in B-cell lymphoma.

D E F

Translocation 1;19 and translocation 8;14 a higher risk of relapse compared to other Ph-negative cases. Genetic
The t(1;19)(q23;p13.3) has been identified in approximately 6 percent of alterations responsible for the activated kinase and cytokine receptor
children with a B-lineage leukemia (see Fig. 13–5). The leukemia cells signaling signature in Ph-like ALL are starting to be elucidated, and
have cytoplasmic immunoglobulin and are CD10+, CD19+, CD34−, include point mutations and gene fusions affecting CRLF2, JAK2, ABL1,
and CD9+. A reciprocal translocation involving the long arms of chro- PDGFRB, EPOR, EBF1, FLT3, IL7R, SH2B3, and other genes. 71
mosomes 8 and 14 [t(8;14)(q24.2;q32.3)] is observed in mature B-cell
ALL (see Fig. 13–5). These patients have a high incidence of central
70
nervous system involvement and/or abdominal nodal involvement at T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA
diagnosis. Although the outcome for both children and adults with a T lymphoblastic leukemia/lymphoma has a distinct pattern of recur-
72
t(8;14) has been poor, the use of high intensity chemotherapy has mark- ring karyotypic abnormalities. Rearrangements involving 14q11.2 (see
edly improved the outcome (EFS of 80 percent in children). 70 Fig. 13–5) and two regions of chromosome 7, (7q34) and (7p14), are
particularly frequent in T-cell malignancies (see Table 13–4). The most
Philadelphia Chromosome–like Acute Lymphocytic/ common are the t(10;11)(q24.3;q11.2) (7 percent of childhood and
Lymphoblastic Leukemia 30 percent of adult cases, TLX1 gene); the cryptic t(5;14)(q35.1;q32.1)
Ph-like ALL is a novel subgroup of high-risk ALL, characterized by (TLX3, 20 percent of childhood and 10 to 15 percent of adult cases),
increased expression of HSC genes, and a similar gene expression profile t(11;14) (p13;q11.2) (approximately 3 percent, LMO2 gene), and t(7;9)
to Ph-positive ALL. Like Ph-positive ALL, Ph-like cases are also char- (q34;q34.3) (approximately 2 percent, NOTCH1 gene). Approximately
acterized by a high frequency of IKZF1 deletions and mutations, which 30 percent of patients have activating mutations of the NOTCH1 gene.
confer a poor prognosis. Ph-like ALL comprises up to 15 percent of Patients with T-cell ALL are most often young males and often have
9,10
pediatric ALL and up to 30 percent of adult ALL and is associated with a mediastinal tumor mass, high white blood cell count, and leukemia

ALL NHL
Normal
Normal 5% t(8;14)
Other 20% 5%
25%
Other
44%
>50 chs t(12;21) t(14;18)
5% 5% 25%

t(8;14)
5%
t(11q23) t(9;22)
5% t(4;11) 30% t(2;5)
3%
5% t(11;18) t(11;14) t(3q27)
3% 5% 10%
Figure 13–6. Frequency of recurring abnormalities in acute lymphocytic/lymphoblastic leukemias (ALL) and non-Hodgkin lymphomas (NHL).

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