Sign in →

Test Code TALLF T-Cell Acute Lymphoblastic Leukemia (T-ALL), FISH

Useful For

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

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
_I099 Interphases, 25-99 No, (Bill Only) No
_I300 Interphases, >=100 No, (Bill Only) No
_IL25 Interphases, <25 No, (Bill Only) No
_PADD Probe, +1 No, (Bill Only) No
_PB02 Probe, +2 No, (Bill Only) No
_PB03 Probe, +3 No, (Bill Only) No
_PBCT Probe, +2 No, (Bill Only) No

Testing Algorithm

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.

Method Name

Fluorescence In Situ Hybridization (FISH)

Reporting Name

ALL (T-cell), FISH

Specimen Type

Varies


Shipping Instructions


Advise Express Mail or equivalent if not on courier service.



Necessary Information


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.



Specimen Required


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.


Specimen Minimum Volume

Blood: 2 mL; Bone Marrow: 1 mL

Specimen Stability Information

Specimen Type Temperature Time
Varies Ambient (preferred)
  Refrigerated 

Reject Due To

No specimen should be rejected.

Clinical Information

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 (≥4 abnormalities)

 

Reference Values

An interpretive report will be provided.

Interpretation

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

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).

 

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

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

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

Method Description

This test is performed using commercially available and laboratory-developed probes. Deletion of the CDKN2A locus on chromosome 9 and TP53 on chromosome 17 are detected using enumeration strategy probes. Rearrangements involving TAL1/STIL, TRB, MLL (KMT2A), and TRAD are detected using dual-color break-apart (BAP) strategy probes. Dual-color, dual-fusion (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) is detected using a D-FISH probe strategy. For enumeration and BAP strategy probe sets, 200 interphase nuclei are scored; 500 interphase nuclei are scored when D-FISH probes are used. Two technologists analyze each probe set and all results are expressed as the percent abnormal nuclei.(Unpublished Mayo method)

Day(s) and Time(s) Performed

Specimens are processed Monday through Sunday. Results reported Monday through Friday, 8 a.m.-5 p.m.

Analytic Time

7 days

Specimen Retention Time

4 weeks

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

88271 x 2, 88291-DNA probe, each (first probe set), Interpretation and report

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

88271-DNA probe, each; coverage for sets containing 3 probes (if appropriate)

88271 x 2-DNA probe, each; coverage for sets containing 4 probes (if appropriate)

88271 x 3-DNA probe, each; coverage for sets containing 5 probes (if appropriate)

88274 w/modifier 52-Interphase in situ hybridization, <25 cells, each probe set (if appropriate)

88274-Interphase in situ hybridization, 25 to 99 cells, each probe set (if appropriate)        

88275-Interphase in situ hybridization, 100 to 300 cells, each probe set (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
TALLF ALL (T-cell), FISH In Process

 

Result ID Test Result Name Result LOINC Value
51924 Result Summary 50397-9
51926 Interpretation 69965-2
51925 Result Table No LOINC Needed
54551 Result In Process
CG692 Reason for Referral 42349-1
CG693 Specimen 31208-2
51927 Source 31208-2
51928 Method 49549-9
55117 Additional Information 48767-8
53863 Disclaimer 62364-5
51929 Released By 18771-6

Forms

If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request Form (T726) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/hematopathology-request-form.pdf)