Test Id : TALAF

This test includes a charge for the probe application, analysis, and professional interpretation of results for 10 probe sets (20 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.

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.

The diagnostic adult T-cell acute lymphoblastic leukemia (T-ALL) FISH panel includes testing for the following abnormalities using the following FISH probes:

9p24.1 rearrangement, JAK2 break-apart

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

11q23 rearrangement, MLL (KMT2A) break-apart

1p33 rearrangement, TAL1/STIL

t(5;14), TLX3/BCL11B fusion

7q34 rearrangement, TRB break-apart

14q11.2 rearrangement, TRAD break-apart

t(10;11), MLLT10/PICALM fusion

9q34 rearrangement, ABL1 break-apart

5q32 rearrangement, PDGFRB break-apart

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(AFDN)/MLL

t(9;11)(p22;q23) MLLT3/MLL

t(10;11)(p12;q23) MLLT10/MLL

t(11;19)(q23;p13.1) MLL/ELL

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(10;14)(q24;q11.2) TLX1/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/TLX1 or t(7;11)(q34;p13) TRB/LMO2.

For more information see Acute Leukemias of Ambiguous Lineage Testing Algorithm.

This test is only performed on specimens from patients with T-cell acute lymphoblastic leukemia (T-ALL) who are 31 years and older.

This test is intended for instances when the entire T- ALL fluorescence in situ hybridization (FISH) panel is needed for an adult patient.

-If this test is ordered on a patient 30 years of age or younger, this test will be canceled and automatically reordered by the laboratory as TALPF / T-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies.

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

-If BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Adult, FISH, Varies is ordered concurrently with this test, the laboratory may cancel TALAF and automatically reorder as TALMF / T-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies with the following FISH probes: TLX3/BCL11B, break-apart TRB, break-apart TRAD, MLLT10/PICALM, TAL1/STIL. If an abnormality is identified that would result in reflex testing in TALAF, the same reflex testing will be performed in the TALMF. This cancellation is necessary to avoid duplicate testing. Probes for break-apart PDGFRB, break-apart JAK2, CDKN2A/D9Z1, ABL1/BCR, break-apart ABL1, break-apart MLL, TP53/D17Z1 will still be performed as part of the adult B-ALL FISH panel.

If limited T-cell ALL FISH probes are preferred, order TALMF / T-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies.

At follow-up, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and targeted T-ALL FISH probes can be evaluated based on the abnormalities identified in the diagnostic study. Order TALMF / T-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies and request specific probes or abnormalities.

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.

For patients with T-cell lymphoma, order TLPDF / T-Cell Lymphoma, Diagnostic FISH, Varies.

For testing paraffin-embedded tissue samples from patients with T-cell lymphoblastic lymphoma, order TLBLF / T-Lymphoblastic Leukemia/Lymphoma, FISH, Tissue. If a paraffin-embedded tissue sample is submitted for this test, testing will be canceled and TLBLF will be added and performed as the appropriate test.

At diagnosis, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and this fluorescence in situ hybridization (FISH) panel should be performed. If there is limited specimen available, only this test will be performed.

Advise Express Mail or equivalent if not on courier service.

A reason for testing and a flow cytometry and/or a bone marrow pathology report should be submitted with each specimen. The laboratory will not reject testing if this information is not provided; however, appropriate testing and interpretation may be compromised or delayed. If not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.

Submit only 1 of the following specimens:

Preferred

Specimen Type: Bone marrow

Container/Tube:

Preferred: Yellow top (ACD)

Acceptable: Green top (heparin) or lavender top (EDTA)

Specimen Volume: 2 to 3 mL

Collection Instructions:

1. It is preferable to send the first aspirate from the bone marrow collection.

2. Invert several times to mix bone marrow.

3. Send bone marrow specimen in original tube. Do not aliquot.

Acceptable

Specimen Type: Blood

Container/Tube:

Preferred: Yellow top (ACD)

Acceptable: Green top (heparin) or lavender top (EDTA)

Specimen Volume: 6 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

• Acute Leukemias of Ambiguous Lineage Testing Algorithm

If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.

Blood: 2 mL

Bone Marrow: 1 mL

Detecting a neoplastic clone associated with the common chromosome abnormalities and classic rearrangements observed in adult patients with T-cell acute lymphoblastic leukemia (T-ALL)

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

This test includes a charge for the probe application, analysis, and professional interpretation of results for 10 probe sets (20 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.

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.

The diagnostic adult T-cell acute lymphoblastic leukemia (T-ALL) FISH panel includes testing for the following abnormalities using the following FISH probes:

9p24.1 rearrangement, JAK2 break-apart

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

11q23 rearrangement, MLL (KMT2A) break-apart

1p33 rearrangement, TAL1/STIL

t(5;14), TLX3/BCL11B fusion

7q34 rearrangement, TRB break-apart

14q11.2 rearrangement, TRAD break-apart

t(10;11), MLLT10/PICALM fusion

9q34 rearrangement, ABL1 break-apart

5q32 rearrangement, PDGFRB break-apart

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(AFDN)/MLL

t(9;11)(p22;q23) MLLT3/MLL

t(10;11)(p12;q23) MLLT10/MLL

t(11;19)(q23;p13.1) MLL/ELL

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(10;14)(q24;q11.2) TLX1/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/TLX1 or t(7;11)(q34;p13) TRB/LMO2.

For more information see Acute Leukemias of Ambiguous Lineage Testing Algorithm.

T-cell acute lymphoblastic leukemia (T-ALL) accounts for approximately 25% of cases of adult lymphoblastic leukemia. Specific genetic abnormalities are identified in most cases of T-ALL, although many of the classic abnormalities are "cryptic" by conventional chromosome studies and must be identified by fluorescence in situ hybridization (FISH) studies. Each of the genetic subgroups is important to detect and can be critical prognostic markers.

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 is listed in the following table.

Table. Common Chromosome Abnormalities in T-cell Acute Lymphoblastic Leukemia

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.

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

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

Fluorescence in situ hybridization (FISH) is not a substitute for conventional chromosome studies because the latter detects chromosome abnormalities associated with other hematological disorders that would go undetected by this FISH panel test.

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 neoplastic cells in the blood specimen (as verified by a hematopathologist).

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. Each probe set was evaluated to confirm the probe set detected the abnormality it was designed to detect.

1. T-lymphoblastic leukaemia/lymphoma. In: Swerdlow SH, Campo E, Harris NL, et al, eds: WHO Classification of Tumours. Vol 2. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. IARC Press; 2017:209-213

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(4):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, Vandenberghe, P, Hagemeijer A: 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, Stern MH, Sigaux F. 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

This test is performed using commercially available and laboratory-developed probes. Rearrangements involving TAL1/STIL, PDGFRB, TRB, JAK2, ABL1, MLL (KMT2A), and TRAD are detected using dual-color break-apart (BAP) strategy probes. Dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) strategy probe sets are used to detect t(5;14), t(9;22), t(10;11), and in reflex testing when rearrangements of MLL, TRB, or TRAD genes are detected. Amplification of the ABL1 (9q34) gene region is detected using a D-FISH probe strategy. For enumeration and BAP strategy probe sets, 100 interphase nuclei are scored; 200 interphase nuclei are scored when D-FISH probes are used. All results are expressed as the percent abnormal nuclei.(Unpublished Mayo method)

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This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

88271x20, 88275x10, 88291x1-FISH Probe, Analysis, Interpretation; 10 probe sets

88271x2, 88275x1-FISH Probe, Analysis; each additional probe set (if appropriate)