Detecting a neoplastic clone associated with the common chromosome abnormalities and classic rearrangements seen in adult patients with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL)
An adjunct to conventional chromosome studies for patients with B-ALL/LBL
Evaluating specimens in which standard cytogenetic analysis is unsuccessful
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
BALAB | Probe, Each Additional (BALAF) | No, (Bill Only) | No |
BAL3B | Probe, Tri-color (BAL) | No, (Bill Only) | No |
The initial panel includes testing for the following abnormalities using the probes listed:
t(9;22), BCR/ABL1
t(X;14)(p22.33;q32)/ t(Y;14)(p11.32;q32), CRLF2/IGH
If results for the initial panel are negative, the following reflex probe sets will be performed as a secondary panel:
1q25 rearrangement, ABL2 break-apart
5q32 rearrangement, PDGFRB break-apart
9p24.1 rearrangement, JAK2 break-apart
9q34 rearrangement, ABL1 break-apart
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement
Finally, if results for the secondary panel are negative, the following probe sets will be performed as a tertiary panel:
t(1;19)(q23;p13), PBX1/TCF3 fusion
Hyperdiploidy, +4,+10,+17: D4Z1/D10Z1/D17Z1
t(12;21)(p13;q22), ETV6/RUNX1 & iAMP21
14q32 rearrangement, IGH break-apart
11q23 rearrangement, MLL(KMT2A) break-apart
When a KMT2A (MLL) rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of:
t(4;11)(q21;q23) AFF1/MLL
MLLT4(AFDN)/MLL
t(6;11)(q27;q23)
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
Fore more information, see B-Lymphoblastic Leukemia/Lymphoma Algorithm.
Fluorescence In Situ Hybridization (FISH)
+4,+10,+17
17p- (17p deletion) or TP53
9p- (9p deletion) or CDKN2A or p16
ABL1 (9q34) rearrangement
ABL2 (1q25) rearrangement
BCR-ABL1 like ALL
CRLF2 (Xp22.33) or (Yp11.32) rearrangement
Hyperdiploidy
Hypodiploid/pseudo-hyperdiploid
Hypotriploid/Near-Triploid
iAMP21
IGH (14q32) rearrangement
IKZF1 deletion
JAK2 (9p24.1) rearrangement
MLL or KMT2A (11q23) rearrangement
P2RY8 (Xp22.33) or (Yp11.32) rearrangement
Ph-like ALL
Philadelphia-like ALL
t(1;19)(q23;p13.3) - PBX1/TCF3
t(10;11)(p12;q23) - MLLT10/MLL or AF10/MLL
t(11;19)(q23;p13.1) - MLL/ELL
t(11;19)(q23;p13.3) - MLL/MLLT1 or MLL/ENL
t(12;21)(p13;q22) - TEL/AML1 or ETV6/RUNX1
t(4;11)(q21;q23) - AFF1/MLL or AF4/MLL
t(6;11)(q27;q23) - MLLT4(AFDN)/MLL or AF6/MLL
t(9;11)(p22;q23) - MLLT3/MLL or AF9/MLL
t(9;22)(9q34;q11.2) - BCR/ABL1
t(X;14)(p22.3;q32) - CRLF2/IGH
t(Y;14)(p11.32;q32) - CRLF2/IGH
PDGFRB (5q32) rearrangement
The initial panel includes testing for the following abnormalities using the probes listed:
t(9;22), BCR/ABL1
t(X;14)(p22.33;q32)/ t(Y;14)(p11.32;q32), CRLF2/IGH
If results for the initial panel are negative, the following reflex probe sets will be performed as a secondary panel:
1q25 rearrangement, ABL2 break-apart
5q32 rearrangement, PDGFRB break-apart
9p24.1 rearrangement, JAK2 break-apart
9q34 rearrangement, ABL1 break-apart
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement
Finally, if results for the secondary panel are negative, the following probe sets will be performed as a tertiary panel:
t(1;19)(q23;p13), PBX1/TCF3 fusion
Hyperdiploidy, +4,+10,+17: D4Z1/D10Z1/D17Z1
t(12;21)(p13;q22), ETV6/RUNX1 & iAMP21
14q32 rearrangement, IGH break-apart
11q23 rearrangement, MLL(KMT2A) break-apart
When a KMT2A (MLL) rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of:
t(4;11)(q21;q23) AFF1/MLL
MLLT4(AFDN)/MLL
t(6;11)(q27;q23)
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
Fore more information, see B-Lymphoblastic Leukemia/Lymphoma Algorithm.
Varies
This test is only performed on specimens from patients with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL) who are 31 years of age or older.
This test is intended to be ordered when the entire B-ALL/LBL 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 BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Pediatric, FISH, 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 COGBF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Children's Oncology Group Enrollment Testing, FISH, Varies
If PHLDF / Philadelphia Chromosome-like Acute Lymphoblastic Leukemia (Ph-like ALL), Diagnostic FISH, Varies, is ordered concurrently with this test, PHLDF testing will be canceled. The probes offered in PHLDF are included within this test, when appropriate.
If limited B-cell ALL FISH probes are preferred, order BALMF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies.
At follow-up, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and targeted B-ALL FISH probes can be evaluated based on the abnormalities identified in the diagnostic study. Order BALMF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies and request specific probes or abnormalities.
If the patient clinically relapses, a conventional chromosome study may be useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a new therapy-related myeloid clone.
For patients with B-cell lymphoma, order BLPMF / B-Cell Lymphoma, Specified FISH, Varies.
For testing paraffin-embedded tissue samples from patients with B-ALL/LBL, order BLBLF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma, FISH, Tissue. If a paraffin-embedded tissue sample is submitted for this test, it will be canceled and BLBLF will be added and performed as the appropriate test.
At diagnosis, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and this panel should be performed per National Comprehensive Cancer Network guidelines. 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 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 in some instances. If not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.
Question ID | Description | Answers |
---|---|---|
GC065 | Reason for Referral | |
GC066 | Specimen |
Whole blood ACD Bone marrow ACD Whole blood Na Hep Bone marrow Na Hep Whole blood EDTA Bone marrow EDTA |
Submit only 1 of the following specimens:
Specimen Type: Bone marrow
Container/Tube:
Preferred: Yellow top (ACD)
Acceptable: Green top (heparin) or lavender top (EDTA)
Specimen Volume: 2-3 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.
If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.
Blood: 2 mL
Bone Marrow: 1 mL
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Varies | Ambient (preferred) | ||
Refrigerated |
Detecting a neoplastic clone associated with the common chromosome abnormalities and classic rearrangements seen in adult patients with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL)
An adjunct to conventional chromosome studies for patients with B-ALL/LBL
Evaluating specimens in which standard cytogenetic analysis is unsuccessful
The initial panel includes testing for the following abnormalities using the probes listed:
t(9;22), BCR/ABL1
t(X;14)(p22.33;q32)/ t(Y;14)(p11.32;q32), CRLF2/IGH
If results for the initial panel are negative, the following reflex probe sets will be performed as a secondary panel:
1q25 rearrangement, ABL2 break-apart
5q32 rearrangement, PDGFRB break-apart
9p24.1 rearrangement, JAK2 break-apart
9q34 rearrangement, ABL1 break-apart
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement
Finally, if results for the secondary panel are negative, the following probe sets will be performed as a tertiary panel:
t(1;19)(q23;p13), PBX1/TCF3 fusion
Hyperdiploidy, +4,+10,+17: D4Z1/D10Z1/D17Z1
t(12;21)(p13;q22), ETV6/RUNX1 & iAMP21
14q32 rearrangement, IGH break-apart
11q23 rearrangement, MLL(KMT2A) break-apart
When a KMT2A (MLL) rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of:
t(4;11)(q21;q23) AFF1/MLL
MLLT4(AFDN)/MLL
t(6;11)(q27;q23)
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
Fore more information, see B-Lymphoblastic Leukemia/Lymphoma Algorithm.
In the United States, the incidence of acute lymphoblastic leukemia (ALL) is roughly 6000 new cases per year (as of 2019). ALL accounts for approximately 70% of all childhood leukemia cases (ages 0-19 years), making it the most common type of childhood cancer. Approximately 85% of pediatric cases of ALL are of B-cell lineage (B-ALL) and 15% are of T-cell lineage. It has a peak incidence at 2 to 5 years of age. The incidence decreases with increasing age, before increasing again at around 50 years of age. ALL is slightly more common in male patients than female patients. There is an increased incidence of ALL in individuals with Down syndrome, Fanconi anemia, Bloom syndrome, ataxia telangiectasia, X-linked agammaglobulinemia, and severe combined immunodeficiency. The overall cure rate for ALL in children is about 90%, and about 45% to 60% of adults have long-term disease-free survival. CRLF2/IGH rearrangements are more commonly observed in patients with Down syndrome or of Hispanic descent.
Specific genetic abnormalities are identified in the majority of cases of B-ALL, either by conventional chromosome studies or fluorescence in situ hybridization (FISH) studies. Each of the B-ALL genetic subgroups is important to detect and can be critical prognostic markers. The decision for early transplantation may be made if t(9;22)(q34;q11.2), MLL (KMT2A) translocations, RUNX1 duplication/amplification (iAMP21) or a hypodiploid clone is identified. In contrast, if the ETV6/RUNX1 fusion is detected by FISH or hyperdiploidy is identified by chromosome studies, the patient has a favorable prognosis and transplantation is rarely considered.
A newly recognized World Health Organization entity BCR-ABL1-like ALL, also known as Philadelphia chromosome-like acute lymphoblastic leukemia, is increasing in importance due to the poor prognosis seen in pediatric, adolescent, and young adult ALL. Common features of this entity involve rearrangements with tyrosine kinase genes involving the following genes: ABL2, PDGFRB, JAK2, ABL1, CRLF2, and P2RY8. Deletion of IKZF1 often accompanies this entity. Some patients who have failed conventional therapies have demonstrated favorable responses to targeted therapies in clinical trials when rearrangements involving these specific gene regions have been identified.
Evaluation of the MYC gene region is included in all diagnostic B-ALL panels to evaluate for Burkitt lymphoma. If a positive result is obtained, additional testing for the BCL2 and BCL6 gene regions will be performed.
Per National Comprehensive Cancer Network guidelines, a combination of cytogenetic and FISH testing is currently recommended in all pediatric and adult patients with B-ALL/lymphoblastic lymphoma (LBL). Additional cytogenetic techniques such as chromosomal microarray (CMAH / Chromosomal Microarray, Hematologic Disorders, Varies) may be helpful to resolve questions related to ploidy (hyperdiploid clone vs doubled hypodiploid clone) or to resolve certain clonal structural rearrangements such as the presence or absence of intra-chromosomal amplification of chromosome 21 (iAMP21). A summary of the characteristic chromosome abnormalities identified in B-ALL is listed in the following table. A summary of the characteristic chromosome abnormalities identified in B-ALL is listed in the following table.
Table. Common Chromosome Abnormalities in B-cell Acute Lymphoblastic Leukemia
Cytogenetic change | Typical demographic | Risk category | |
B-acute lymphoblastic leukemia | t(12;21)(p13;q22), ETV6/RUNX1 | Pediatric | Favorable |
Hyperdiploidy | Pediatric | Favorable | |
t(1;19)(q23;p13.3), PBX1/TCF3 | Pediatric | Intermediate to favorable | |
t(9;22)(q34;q11.2), BCR/ABL1 | All ages | Unfavorable | |
iAMP21, RUNX1 | Pediatric | Unfavorable | |
del(9p), CDKN2A | All ages | Unknown | |
t(11q23;var), MLL | All ages | Unfavorable | |
t(4;11)(q21;q23), AFF1/MLL | All ages | Unfavorable | |
t(6;11)(q27;q23), MLLT4(AFDN)/MLL | All ages | Unfavorable | |
t(9;11)(p22;q23), MLLT3/MLL | All ages | Unfavorable | |
t(10;11)(p12;q23), MLLT10/MLL | All ages | Unfavorable | |
t(11;19)(q23;p13.1), MLL/ELL | All ages | Unfavorable | |
t(11;19)(q23;p13.3), MLL/MLLT1 | All ages | Unfavorable | |
t(14q32;var), IGH | All ages | Variable | |
t(X;14)(p22;q32)/t(Y;14)(p11;q32), CRLF2/IGH | Adolescent/ young adult | Unfavorable | |
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 | All ages | Unfavorable | |
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 | All ages | Unfavorable | |
-17/17p-, TP53 | All ages | Unfavorable | |
t(8q24.1;var), MYC | Pediatric/ adolescent/ young adult | ||
Complex karyotype (> or =4 abnormalities) | Adult | Unfavorable | |
Low hypodiploidy/near triploidy | Adult | Unfavorable | |
Near-haploid/hypodiploid | All ages | Unfavorable | |
del(7p) IKZF1 | All ages | Unfavorable in absence of ERG deletion | |
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) | t(1q25;var), ABL2 | Pediatric/ adolescent/ young adult | Unfavorable |
t(5q32;var), PDGFRB | |||
t(9p24.1;var), JAK2 | |||
t(9q34;var), ABL1 | |||
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 | |||
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 |
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 be missed by this FISH panel test.
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. Moorman AV, Harrison CJ, Buck GA, et al: Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007 Apr 15;109(8):3189-3197. doi: 10.1182/blood-2006-10-051912
2. Moorman AV: The clinical relevance of chromosomal and genetic abnormalities in B-cell precursor acute lymphoblastic leukemia. Blood Rev. 2012;26:123-135. doi: 10.1016/j.blre.2012.01.001
3. Roberts KG, Li Y, Payne-Turner D, et al: Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014 Sept;371(11):1005-1015. i: 10.1056/NEJMoa1403088
4. Mullighan CG: The genomic landscape of acute lymphoblastic leukemia in children and young adults. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):174-180. doi: 10.1182/asheducation-2014.1.174
This test is performed using commercially available and laboratory-developed probes. Deletion of the CDKN2A locus on chromosome 9, TP53 on chromosome 17, deletion of IKZF1 on chromosome 7, and gain of chromosomes 4, 10, and 17 are detected using enumeration strategy probes. Rearrangements involving ABL2, PDGFRB, MYC, JAK2, ABL1, MLL, IGH, CRLF2, and P2RY8 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(X/Y;14), t(9;22), t(12;21), t(1;19), and in reflex testing when rearrangements of the MLL and IGH genes are detected. Amplification of RUNX1 (21q22) 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. Results are expressed as the percent abnormal nuclei.(Unpublished Mayo method)
Monday through Friday
This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
88271 x4,88275 x2, 88291 - FISH Probe, Analysis, Interpretation; 2 probe sets
88271 x2, 88275 - FISH Probe, Analysis; each additional probe set (if appropriate)
88271 - FISH Probe (if appropriate)
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
BALAF | Adult ALL (B-cell), FISH | In Process |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
609538 | Result Summary | 50397-9 |
609539 | Interpretation | 69965-2 |
609540 | Result Table | 93356-4 |
609541 | Result | 62356-1 |
GC065 | Reason for Referral | 42349-1 |
GC066 | Specimen | 31208-2 |
609542 | Source | 31208-2 |
609543 | Method | 85069-3 |
609544 | Additional Information | 48767-8 |
609545 | Disclaimer | 62364-5 |
609546 | Released By | 18771-6 |
Change Type | Effective Date |
---|---|
New Test | 2021-12-13 |