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. 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.

This test is performed as panel testing only using the following analysis algorithm.

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 FISH probes listed:

t(9p24.1;var) or 9p24.1 rearrangement, JAK2 break-apart

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

t(11q23;var) or 11q23 rearrangement, MLL(KMT2A) break-apart

1p33 rearrangement or STIL deletion, TAL1/STIL

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

t(7q34;var) or 7q34 rearrangement, TRB break-apart

t(14q11.2;var) or 14q11.2 rearrangement, TRAD break-apart

t(10;11)(p12;q14) or MLLT10::PICALM fusion, MLLT10/PICALM fusion

t(9q34;var) or 9q34 rearrangement, ABL1 break-apart

t(5q32;var) or 5q32 rearrangement, PDGFRB break-apart

Appropriate ancillary probes may be performed at consultant discretion to render comprehensive assessment. Any additional probes will have the results included within the final report and will be performed at an additional charge.

When an MLL(KMT2A) rearrangement is identified, appropriate reflex testing will be performed in an attempt to identify the translocation partner. Probes include identification of t(4;11)(q21;q23) AFF1::MLL(KMT2A) fusion, t(6;11)(q27;q23) MLLT4(AFDN)::MLL(KMT2A) fusion, t(9;11)(p22;q23) MLLT3::MLL(KMT2A) fusion, t(10;11)(p12;q23) MLLT10::MLL(KMT2A) fusion, t(11;19)(q23;p13.1) MLL(KMT2A)::ELL fusion or t(11;19)(q23;p13.3) MLL(KMT2A)::MLLT1 fusion. In the event an 11q23 translocation is identified by chromosome analysis, only the targeted MLL reflex probe will be performed if applicable.

When a TRAD(TCR alpha delta) rearrangement is identified, appropriate reflex testing will be performed in an attempt to identify the translocation partner. Probes include identification of t(10;14)(q24;q11.2) TLX1::TRAD fusion or t(11;14)(p13;q11.2) LMO2::TRAD fusion. In the event a 14q11.2 translocation is identified by chromosome analysis, only the targeted TRAD reflex probe will be performed if applicable.

When a TRB(TCR beta) rearrangement is identified, appropriate reflex testing will be performed in an attempt to identify the translocation partner. Probes include identification of t(7;10)(q34;q24) TRB::TLX1 fusion or t(7;11)(q34;p13) TRB::LMO2 fusion. In the event a 7q34 translocation is identified by chromosome analysis, only the targeted TRB reflex probe will be performed if applicable.

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.

This test should NOT be used to screen for residual T-cell acute lymphoblastic leukemia (T-ALL). At follow-up, or if the patient clinically relapses, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) are useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a new therapy-related myeloid clone. Additionally, targeted T-ALL FISH probes can be evaluated based on the abnormalities identified in the diagnostic study.

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

If this test is ordered on a patient 30 years 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 cancelation 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.

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 leukemia/lymphoma (T-LBL), order TLBLF / T-Cell 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.

1.  A reason for testing must be provided. If this information is not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.

2. 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, but appropriate testing and interpretation may be compromised or delayed.

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: Whole 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.

Bone marrow: 1 mL; Whole blood: 2 mL

Detecting, at diagnosis, recurrent common chromosome abnormalities associated with T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) in adult patients

As an adjunct to conventional chromosome studies in patients with T-ALL

Evaluating specimens in which chromosome studies are unsuccessful

This test should not be used to screen for residual 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. 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.

This test is performed as panel testing only using the following analysis algorithm.

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 FISH probes listed:

t(9p24.1;var) or 9p24.1 rearrangement, JAK2 break-apart

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

t(11q23;var) or 11q23 rearrangement, MLL(KMT2A) break-apart

1p33 rearrangement or STIL deletion, TAL1/STIL

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

t(7q34;var) or 7q34 rearrangement, TRB break-apart

t(14q11.2;var) or 14q11.2 rearrangement, TRAD break-apart

t(10;11)(p12;q14) or MLLT10::PICALM fusion, MLLT10/PICALM fusion

t(9q34;var) or 9q34 rearrangement, ABL1 break-apart

t(5q32;var) or 5q32 rearrangement, PDGFRB break-apart

Appropriate ancillary probes may be performed at consultant discretion to render comprehensive assessment. Any additional probes will have the results included within the final report and will be performed at an additional charge.

When an MLL(KMT2A) rearrangement is identified, appropriate reflex testing will be performed in an attempt to identify the translocation partner. Probes include identification of t(4;11)(q21;q23) AFF1::MLL(KMT2A) fusion, t(6;11)(q27;q23) MLLT4(AFDN)::MLL(KMT2A) fusion, t(9;11)(p22;q23) MLLT3::MLL(KMT2A) fusion, t(10;11)(p12;q23) MLLT10::MLL(KMT2A) fusion, t(11;19)(q23;p13.1) MLL(KMT2A)::ELL fusion or t(11;19)(q23;p13.3) MLL(KMT2A)::MLLT1 fusion. In the event an 11q23 translocation is identified by chromosome analysis, only the targeted MLL reflex probe will be performed if applicable.

When a TRAD(TCR alpha delta) rearrangement is identified, appropriate reflex testing will be performed in an attempt to identify the translocation partner. Probes include identification of t(10;14)(q24;q11.2) TLX1::TRAD fusion or t(11;14)(p13;q11.2) LMO2::TRAD fusion. In the event a 14q11.2 translocation is identified by chromosome analysis, only the targeted TRAD reflex probe will be performed if applicable.

When a TRB(TCR beta) rearrangement is identified, appropriate reflex testing will be performed in an attempt to identify the translocation partner. Probes include identification of t(7;10)(q34;q24) TRB::TLX1 fusion or t(7;11)(q34;p13) TRB::LMO2 fusion. In the event a 7q34 translocation is identified by chromosome analysis, only the targeted TRB reflex probe will be performed if applicable.

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. An abnormal karyotype is found in 50% to 70% of T-ALL cases, although many of the classic abnormalities are "cryptic" by conventional chromosome studies and must be identified by fluorescence in situ hybridization studies and are associated with various prognoses. 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 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 set.

The absence of an abnormal clone does not rule out the presence of a 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 in a targeted T-ALL 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 circulating malignant cells in the blood specimen (as verified by a hematopathologist).

If no FISH signals are observed post-hybridization, the case will be released indicating a lack of FISH results.

1. WHO Classification of Tumours Editorial Board, eds. Haematolymphoid tumours. 5th ed. IARC Press; 2024. WHO Classification of Tumours, Volume 11

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 a dual-color break-apart (BAP) strategy probe. 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(KMT2A), TRB, or TRAD genes are detected. Amplification of the ABL1 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)