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HelpMayo Test ID PHLDF Philadelphia Chromosome-like Acute Lymphoblastic Leukemia (Ph-like ALL), Diagnostic FISH, Varies
Ordering Guidance
This test is intended to be ordered when the entire Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like B-cell ALL) fluorescence in situ hybridization (FISH) panel is needed.
If this test is ordered concurrently with either BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies or BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies, this test will be canceled. The probes offered in this test are included within BALAF and BALPF, when appropriate.
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 limited Ph-like B-cell ALL FISH probes are preferred, order BALMF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies.
At diagnosis, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and a complete B-ALL FISH panel, either BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies or BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies, depending on the age of the patient, should be performed.
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 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-cell lymphoblastic lymphoma, order BLBLF / B-Cell Lymphoblastic Leukemia/Lymphoma, FISH, Tissue. If a paraffin-embedded tissue sample is submitted for this test, testing will be canceled and BLBLF will be added and performed as the appropriate test.
Shipping Instructions
Advise Express Mail or equivalent if not on courier service.
Necessary Information
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, but appropriate testing and interpretation may be compromised or delayed in the absence of this information. If not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.
Specimen Required
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: 2-3 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.
Useful For
Detecting a neoplastic clone associated with Philadelphia chromosome-like acute lymphoblastic leukemia (ALL), particularly when a classic abnormality is not detected with the initial panel
An adjunct to conventional chromosome studies in patients with B-cell ALL
Evaluating specimens in which standard cytogenetic analysis is unsuccessful
Testing Algorithm
This test includes a charge for the probe application, analysis, and professional interpretation of results for 7 probe sets (14 individual fluorescence in situ hybridization probes). Additional charges will be incurred for all reflex or additional probe sets performed.
The Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) panel includes testing for the following four kinase-activating chromosome rearrangements, as well as for IKZF1 deletion, which often accompanies Ph-like ALL:
1q25 rearrangement, ABL2
5q32 rearrangement, PDGFRB
9p24.1 rearrangement, JAK2
9q34 rearrangement, ABL1
7p-, IKZF1/CEP7
t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement
t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement
When a CRLF2 rearrangement is identified, reflex testing will be performed using the CRLF2/IGH fusion probe set to identify a potential t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32) cryptic translocation.
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.
For more information see B-Lymphoblastic Leukemia/Lymphoma Algorithm.
Special Instructions
Method Name
Fluorescence In Situ Hybridization (FISH)
Reporting Name
Ph-like ALL(B-cell), Diag FISHSpecimen Type
VariesSpecimen Minimum Volume
Blood: 2 mL
Bone Marrow: 1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Ambient (preferred) | ||
| Refrigerated | |||
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
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 (T-ALL). 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 are 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.
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.
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 a neoplastic disorder.
Cautions
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.
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 a hematopathologist).
Clinical Reference
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
2. Moorman AV: The clinical relevance of chromosomal and genetic abnormalities in B-cell precursor acute lymphoblastic leukemia. Blood. Rev. 2012 May;26(3):123-135
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
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
5. Arber DA, Orazi A, Hasserjian R, et al: The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-2405
Method Description
This test is performed using commercially available and laboratory-developed probes. Deletion of IKZF1 on chromosome 7 is detected using enumeration strategy probes. Rearrangements involving ABL2, PDGFRB, JAK2, ABL1, CRLF2, and P2RY8 are detected using a dual-color break-apart (BAP) strategy probe. A dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) strategy probe set is used to detect t(X/Y;14). 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)
Day(s) Performed
Monday through Friday
Report Available
7 to 10 daysSpecimen Retention Time
4 weeksPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
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.CPT Code Information
88271x14, 88275x7, 88291 x1-FISH Probe, Analysis, Interpretation; 7 probe sets
88271x2, 88275x1-FISH Probe, Analysis; each additional probe set (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| PHLDF | Ph-like ALL(B-cell), Diag FISH | 101664-1 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 609578 | Result Summary | 50397-9 |
| 609579 | Interpretation | 69965-2 |
| 609580 | Result Table | 93356-4 |
| 609581 | Result | 62356-1 |
| GC077 | Reason for Referral | 42349-1 |
| GC078 | Specimen | 31208-2 |
| 609582 | Source | 31208-2 |
| 609583 | Method | 85069-3 |
| 609584 | Additional Information | 48767-8 |
| 609585 | Disclaimer | 62364-5 |
| 609586 | Released By | 18771-6 |