TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: TALLF    
T-Cell Acute Lymphoblastic Leukemia (T-ALL), FISH, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Detecting a neoplastic clone associated with the common chromosome abnormalities seen in patients with T-cell acute lymphoblastic leukemia (T-ALL)

 

Identifying and tracking known chromosome abnormalities in patients with T-ALL and tracking response to therapy

 

An adjunct to conventional chromosome studies in patients with T-ALL

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test includes a charge for application of the first probe set (2 FISH probes) and professional interpretation of results. Additional charges will be incurred for all reflex probes performed. Analysis charges will be incurred based on the number of cells analyzed per probe set. If no cells are available for analysis, no analysis charges will be incurred.

 

We recommend the following testing algorithm for patients with T-cell acute lymphoblastic leukemia (T-ALL):

-At diagnosis, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and a complete T-ALL FISH panel should be performed.

-At follow-up, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and targeted T-ALL FISH probes based on the abnormalities identified in the diagnostic study can be evaluated.

-If the patient clinically relapses, a conventional chromosome study is useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a new therapy-related myeloid clone.

 

Panel includes testing for the following abnormalities using the probes listed:

1p33 rearrangement, TAL1/STIL

t(5;14) TLX3/BCL11B

7q34 rearrangement, TRB

9p-,CDKN2A/D9Z1

t(9;22) or ABL1 amplification, BCR/ABL1

t(10;11), MLLT10/PICALM

11q23 rearrangement, MLL (KMT2A)

14q11.2 rearrangement, TRAD

17p-, TP53/D17Z1

 

When an MLL (KMT2A) rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of t(4;11)(q21;q23) AFF1/MLL, t(6;11)(q27;q23) MLLT4/MLL, t(9;11)(p22;q23) MLLT3/MLL, t(10;11)(p13;q23) MLLT10/MLL, t(11;19)(q23;p13.1) MLL/ELL or t(11;19)(q23;p13.3) MLL/MLLT1.

 

When a TRAD rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of t(8;14)(q24.1;q11.2) MYC/TRAD, t(10;14)(q24;q11.2) TLX1/TRAD, t(11;14)(p15;q11.2) LMO1/TRAD or t(11;14)(p13;q11.2) LMO2/TRAD.

 

When a TRB rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of t(7;10)(q34;q24) TRB/HOX11, t(7;11)(q34;p15) TRB/LMO1, t(7;11)(q34;p13) TRB/LMO2, or t(6;7)(q27;q34) TRB/MYB.

 

In the absence of BCR/ABL1 fusion, when an extra signal for ABL1 is identified, reflex testing will be performed using the ABL1 break-apart probe set to evaluate for the presence or absence of an ABL1 rearrangement.

 

If this test is ordered and the laboratory is informed that the patient is on a COG protocol, this test will be canceled and automatically reordered by the laboratory as COGTF / T-Cell Acute Lymphoblastic Leukemia (T-ALL), Children’s Oncology Group Enrollment Testing, FISH, Varies.

 

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

In the United States, the incidence of acute lymphoblastic leukemia (ALL) is roughly 6,000 new cases per year (as of 2009), or approximately 1 in 50,000. ALL accounts for approximately 70% of all childhood leukemia cases (ages 0 to 19 years), making it the most common type of childhood cancer.

 

Approximately 85% of pediatric cases of ALL are B-cell lineage (B-ALL) and 15% are T-cell lineage (T-ALL). T-ALL is more common in adolescents than younger children and accounts for 25% of adult ALL. When occurring as a primary lymphoblastic lymphoma (LBL), approximately 90% are T-cell lineage versus only 10% B-cell lineage. T-LBL often present as a mediastinal mass in younger patients with or without concurrent bone marrow involvement.

 

Specific genetic abnormalities are identified in the majority of cases of T-ALL, although many of the classic abnormalities are "cryptic" by conventional chromosome studies and must be identified by FISH studies. Each of the genetic subgroups are important to detect and can be critical prognostic markers. One predictive marker, amplification of the ABL1 gene region, has been identified in 5% of T-ALL, and these patients may be responsive to targeted tyrosine kinase inhibitors.

 

A combination of cytogenetic and FISH testing is currently recommended in all pediatric and adult patients to characterize the T-ALL clone for the prognostic genetic subgroups. A summary of the characteristic chromosome abnormalities identified in T-ALL are listed in the following table.

 

Common Chromosome Abnormalities in

T-cell Acute Lymphoblastic Leukemia

Cytogenetic change

Genes involved

del(1p33)

TAL1/STIL

t(5;14)(q35;q32)

TLX3(HOX11L2)/BCL11B

t(10;11)(p13;q14)

MLLT10(AF10)/PICALM

Episomal amplification

ABL1

del(9p)

CDKN2A(p16)

t(11q23;var)

MLL(KMT2A)

t(4;11)(q21;q23)

AFF1(AF4)/MLL(KMT2A)

t(6;11)(q27;q23)

MLLT4(AF6)/MLL(KMT2A)

t(9;11)(p22;q23)

MLLT3(AF9)/MLL(KMT2A)

t(10;11)(p13;q23)

MLLT10(AF10)/MLL(KMT2A)

t(11;19)(q23;p13.1)

MLL(KMT2A)/ELL

t(11;19)(q23;p13.3)

MLL(KMT2A)/MLLT1(ENL)

t(7q34;var)

TRB

t(6;7)(q23;q34)

MYB/TRB

t(7;10)(q34;q24)

TRB/TLX1(HOX11)

t(7;11)(q34;p15)

TRB/LMO1

t(7;11)(q34;p13)

TRB/LMO2

t(14q11.2;var)

TRAD

t(8;14)(q24.1;q11.2)

MYC/TRAD

t(10;14)(q24;q11.2)

TLX1(HOX11)/TRAD

t(11;14)(p15;q11.2)

LMO1/TRAD

t(11;14)(p13;q11.2)

LMO2/TRAD

del(17p)

TP53

Complex karyotype (> or =4 abnormalities)

 

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for any given probe.

 

The absence of an abnormal clone does not rule out the presence of neoplastic disorder.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is not approved by the U.S. Food and Drug Administration and it is best used as an adjunct to existing clinical and pathologic information.

 

Bone marrow is the preferred specimen type for this FISH test. If bone marrow is not available, a blood specimen may be used if there are malignant cells in the blood specimen (as verified by hematopathology).

Supportive Data

Each probe was independently tested and verified on unstimulated peripheral blood and bone marrow specimens. Normal cutoffs were calculated based on the results of 25 normal specimens. For each probe set a series of chromosomally abnormal specimens was evaluated to confirm each probe set detected the abnormality it was designed to detect.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Edited by ES Jaffe, NL Harris, H Stein, JW Vardiman. Lyon, IARC Press, 2001

2. Gesk S, Martin-Subero JI, Harder L, et al: Molecular cytogenetic detection of chromosomal breakpoints in T-cell receptor gene loci. Leukemia 2003;17:738-745

3. Chin M, Mugishima H, Takamura M, et al: Hemophagocytic syndrome and hepatosplenic (gamma)(delta) T-cell lymphoma with isochromosome 7q and 8 trisomy. J Pediatr Hematol Oncol 2004;26(6):375-378

4. Graux C, Cools J, Michaux L, et al: Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast. Leukemia 2006;20:1496-1510

5. Cayuela JM, Madani A, Sanhes L, et al: Multiple tumor-suppressor gene 1 inactivation is the most frequent genetic alteration in T-cell acute lymphoblastic leukemia. Blood 1996;87:2180-2186

6. Hayette S, Tigaud I, Maguer-Satta V, et al: Recurrent involvement of the MLL gene in adult T-lineage acute lymphoblastic leukemia. Blood 2002;99:4647-4649

7. Graux C, Cools J, Melotte C, et al: Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Nat Genet 2004;36:1084-1089