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

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

Tracking known chromosome abnormalities and response to therapy in patients with T-cell acute lymphoblastic leukemia

This panel includes analysis for the disease-associated abnormalities using the 8 probe sets listed below.

1p32, STIL/TAL1

t(5;14)(q35;q32), TLX3/BCL11B

t(7q34;var), TRB

9p-,CDKN2A/9 Cen

t(9;22)(q34;q11.2) or ABL amplification, ABL1/BCR

t(10;11)(p13;q14), MLLT10/PICALM

t(11q23;var), MLL

t(14q11.2;var), TRAD

If abnormalities are detected using either the TRAD or MLL probes, reflex testing will be performed using the following probes sets, respectively:

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

t(11;14)(p13;q11.2), LMO2/TRAD

t(4;11)(q21;q23), AFF1/MLL

t(6;11)(q27;q23), MLLT4/MLL

t(10;11)(p13;q23), MLLT10/MLL

t(11;19)(q23;p13.3), MLL/MLLT1

Unless specified, the 8-probe panel will be run on all specimens. If the patient has been previously identified with a specific abnormality, only those appropriate previously abnormal probe sets will be used to monitor the chromosome anomaly.

When this test is ordered, a charge for 2 FISH probes and interpretation is included. If additional probes or the entire panel are ordered, additional probe charges will be added.

• Cytogenetics Hematologic FISH Panel Patient Information Sheet

Fluorescence In Situ Hybridization (FISH)

Provide a reason for referral with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.

Forms:

1. Cytogenetics Hematologic FISH Panel Patient Information Sheet (Supply T603) in Special Instructions

2. If not ordering electronically, submit a Cytogenetics Hematologic Disorders Request Form (Supply T607) with the specimen.

Advise Express Mail or equivalent if not on courier service.

Submit only 1 of the following specimens:

Specimen Type: Blood

Container/Tube: Green top (sodium heparin)

Specimen Volume: 7-10 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Other anticoagulants are not recommended and are harmful to the viability of the cells.

Specimen Type: Bone marrow

Container/Tube: Green top (sodium heparin)

Specimen Volume: 1-2 mL

Collection Instructions:

1. Invert several times to mix bone marrow.

2. Other anticoagulants are not recommended and are harmful to the viability of the cells.

T-cell malignancies account for approximately 12% of all non-Hodgkin lymphomas. There are several subtypes of T-cell neoplasms: T-cell acute lymphoblastic leukemia (T-ALL), T-cell prolymphocytic leukemia (T-PLL), T-cell large granular lymphocytic leukemia (T-LGL), anaplastic large cell lymphoma (ALCL), peripheral T-cell lymphoma, and various other cutaneous, nodal, and extranodal lymphoma subtypes. The 2 most prevalent lymphoma subtypes are unspecified peripheral T-cell lymphoma (3.7%) and ALCL (2.4%).

T-ALL is a neoplastic disorder of lymphoblasts committed to the T-cell lineage. These malignancies comprise 15% to 20% of acute leukemias. While half of T-ALL patients have normal chromosome studies, molecular cytogenetic analysis can identify abnormalities including:

-Cryptic deletions of CDKN2A.

-Rearrangements involving 1p32 (STIL/TAL1), 7q34 (TRB), 11q23 (MLL), and 14q11.2 (TRAD).

-Chromosomal translocations including t(5;14)(q35;q32), t(9;22)(q34;q11.2), t(10;11)(p13;q14), and various partner genes involved with the MLL and TRAD gene loci.

-Episomal amplification involving the ABL1/NUP214 fusion gene.

These abnormalities may be seen in tissues (ie, lymph nodes), as well as in blood and bone marrow. This assay detects the common chromosome abnormalities observed in T-ALL.

A few common chromosome abnormalities are associated with specific T-cell lymphoma subtypes, including:

-inv(14)(q11q32) and t(14;14)(q11;q32) involving the T-cell leukemia/lymphoma 1 gene (TCL1A) at 14q32

-Translocations involving the ALK gene at 2p23 in ALCL

-Isochromosome 7q and trisomy 8 in hepatosplenic T-cell lymphoma

For blood and bone marrow specimens from patients with T-cell lymphomas, see FRTLP/89040 T-Cell Lymphoma, FISH, Blood or Bone Marrow.

These probes have diagnostic relevance and can also be used to track response to therapy.

An interpretive report will be provided.

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

Detection of an abnormal clone is supportive of a diagnosis of T-cell acute lymphoblastic leukemia (T-ALL). The specific anomaly detected may help subtype the neoplasm.

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

This test should not be ordered on blood and bone marrow specimens from patients with T-cell lymphoma. In these situations, order FRTLP/89040 T-Cell Acute Lymphoma, FISH, Blood or Bone Marrow.

This test is not FDA approved and it is best used as an adjunct to existing clinical and pathologic information.

1. World Heath 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

Identification of deletions of the p16 locus on chromosome 9 is based on a FISH enumeration strategy. Rearrangements of the STIL/TAL1, TRB, MLL, and TRAD locus on 1p32, 7q34, 11q23, and 14q11.2, respectively, are detected using a dual-color, break-apart (BAP) probe strategy. Dual-color, dual-fusion (D-FISH) probe strategies are used to detect t(5;14)(q35;q32), t(9;22)(q34;q11.2), t(10;11)(p13;q14), and in reflex testing when rearrangements of MLL and TRAD gene loci are detected. Amplification of the ABL1 gene on chromosome band 9q34 is detected using a D-FISH probe strategy. For the enumeration and BAP probe sets, 200 interphase nuclei are scored and for the D-FISH probe sets, 500 interphase nuclei are scored. Results for each abnormal probe set are expressed as percent abnormal nuclei. (Unpublished Mayo method)

Samples processed Monday through Sunday. Results reported Monday through Friday, 8 a.m.-5 p.m. CST.

T-Cell Acute Lymphoblastic Leukemia (T-ALL), FISH

88271 x 2-DNA probe, each

88275 x 2-Interphase in situ hybridization

88291-Interpretation and report

One Additional FISH Probe

88271-DNA probe, each (if appropriate)

88275-Interphase in situ hybridization (if appropriate)

Two Additional FISH Probes

88271 x 2-DNA probe, each (if appropriate)

88275-Interphase in situ hybridization (if appropriate)

Three Additional FISH Probes

88271 x 3-DNA probe, each (if appropriate)

88275-Interphase in situ hybridization (if appropriate)

Four Additional FISH Probes

88271 x 4-DNA probe, each (if appropriate)

88275 x 2-Interphase in situ hybridization (if appropriate)

Five Additional FISH Probes

88271 x 5-DNA probe, each (if appropriate)

88275 x 2-Interphase in situ hybridization (if appropriate)

Six Additional FISH Probes

88271 x 6-DNA probe, each (if appropriate)

88275 x 3-Interphase in situ hybridization (if appropriate)

Seven Additional FISH Probes

88271 x 7-DNA probe, each (if appropriate)

88275 x 3-Interphase in situ hybridization (if appropriate)

Eight Additional FISH Probes

88271 x 8-DNA probe, each (if appropriate)

88275 x 4-Interphase in situ hybridization (if appropriate)

Nine Additional FISH Probes

88271 x 9-DNA probe, each (if appropriate)

88275 x 4-Interphase in situ hybridization (if appropriate)

Ten Additional FISH Probes

88271 x 10-DNA probe, each (if appropriate)

88275 x 5-Interphase in situ hybridization (if appropriate)

Eleven Additional FISH Probes

88271 x 11-DNA probe, each (if appropriate)

88275 x 5-Interphase in situ hybridization (if appropriate)

Twelve Additional FISH Probes

88271 x 12-DNA probe, each (if appropriate)

88275 x 6-Interphase in situ hybridization (if appropriate)

Thirteen Additional FISH Probes

88271 x 13-DNA probe, each (if appropriate)

88275 x 6-Interphase in situ hybridization (if appropriate)

Fourteen Additional FISH Probes

88271 x 14-DNA probe, each (if appropriate)

88275 x 7-Interphase in situ hybridization (if appropriate)

Fifteen Additional FISH Probes

88271 x 15-DNA probe, each (if appropriate)

88275 x 7-Interphase in situ hybridization (if appropriate)

Sixteen Additional FISH Probes

88271 x 16-DNA probe, each (if appropriate)

88275 x 8-Interphase in situ hybridization (if appropriate)

Seventeen Additional FISH Probes

88271 x 17-DNA probe, each (if appropriate)

88275 x 8-Interphase in situ hybridization (if appropriate)

Eighteen Additional FISH Probes

88271 x 18-DNA probe, each (if appropriate)

88275 x 9-Interphase in situ hybridization (if appropriate)

Nineteen Additional FISH Probes

88271 x 19-DNA probe, each (if appropriate)

88275 x 9-Interphase in situ hybridization (if appropriate)

Twenty Additional FISH Probes

88271 x 20-DNA probe, each (if appropriate)

88275 x 10-Interphase in situ hybridization (if appropriate)

Twenty One Additional FISH Probes

88271 x21-DNA probe, each (if appropriate)

88275 x10-Interphase in situ hybridization (if appropriate)

Twenty Two Additional FISH Probes

88271 x22-DNA probe, each (if appropriate)

88275 x11-Interphase in situ hybridization (if appropriate)

Twenty Three Additional FISH Probes

88271 x23-DNA probe, each (if appropriate)

88275 x11-Interphase in situ hybridization (if appropriate)

Twenty Four Additional FISH Probes

88271 x24-DNA probe, each (if appropriate)

88275 x12-Interphase in situ hybridization (if appropriate)

Twenty Five Additional FISH Probes

88271 x25-DNA probe, each (if appropriate)

88275 x12-Interphase in situ hybridization (if appropriate)

Twenty Six Additional FISH Probes

88271 x26-DNA probe, each (if appropriate)

88275 x13-Interphase in situ hybridization (if appropriate)

Twenty Seven Additional FISH Probes

88271 x27-DNA probe, each (if appropriate)

88275 x13-Interphase in situ hybridization (if appropriate)

Twenty Eight Additional FISH Probes

88271 x28-DNA probe, each (if appropriate)

88275 x14-Interphase in situ hybridization (if appropriate)

Twenty Nine Additional FISH Probes

88271 x29-DNA probe, each (if appropriate)

88275 x14-Interphase in situ hybridization (if appropriate)

Thirty Additional FISH Probes

88271 x30-DNA probe, each (if appropriate)

88275 x15-Interphase in situ hybridization (if appropriate)